Stroke Etiology Research Articles

Abstract TP209: Prevalence of Spontaneous Recanalization of Internal Carotid Occlusion: A Systematic Scoping Review

Introduction: Spontaneous recanalization of occluded internal carotid arteries (ICAs) is thought to be an uncommon etiology of recurrent ischemic stroke. However, there is a growing number of reports describing this phenomenon, suggesting that follow-up investigations and/or intervention may be warranted. Our objective was to perform a scoping review of the literature to estimate the prevalence of spontaneous ICA recanalization and the timing of recanalization, and to describe imaging modalities used in follow-up as well as any post-recanalization interventions. Methods: MEDLINE, Embase, Cochrane Central Register of Controlled Trials and Web of Science were searched from inception to June 2022 for studies that included adults with spontaneous recanalization or transient occlusion of the internal carotid artery. Two investigators independently screened the studies and extracted data around recanalization prevalence, timepoints, imaging, and treatment. These results were described qualitatively, and descriptive statistics were calculated where appropriate. Results: Among the 2384 studies retrieved, 51 met inclusion criteria, of which 34 were case studies and 17 were cohort studies, with a total of 816 patients. Prevalence of recanalization was reported in 20 studies (3 case studies, 17 cohort studies) at a median of 40.0% (IQR 22.5 - 40.0%) in case studies, and 21.2% (IQR 9.2 - 37.5%) in cohort studies. Forty-one studies reported a time frame for when recanalization was identified, with 53.7% individual cases in case studies and 33.3% amongst cohort studies identified within the first 3 months after occlusion. When reported, antiplatelet treatment was the most common medical treatment pre- and post-recanalization with 189 and 36 individuals, respectively. Finally, doppler imaging was used in 70.6% of studies to identify recanalization, with angiography as the next most common modality at 54.9%. Twenty studies reported an endovascular intervention. Conclusions: Spontaneous recanalization occurs more commonly than previously thought. Currently there is no consensus on what intervention is needed (if any), or when this intervention would occur. More data is needed to confirm this data and determine the best time frame to re-image.

Abstract TMP48: Long-Term Cardiac Monitoring in Cryptogenic Stroke: The San Diego Experience

Purpose: Approximately 30% of all ischemic stroke (AIS) etiology is identified as cryptogenic. Implantable cardiac monitors (ICM) have become increasingly utilized based on results of the CRYSTAL-AF trial. Furthermore, this is now supported by current AHA guidelines. The purpose of this study was to assess the real-world reliability and experience of ICM in two large, academic Comprehensive Stroke Centers (CSC). Methods: We performed a retrospective review of prospectively collected data in two large, academic CSCs (UCSD Hillcrest Medical Center and UCSD Jacobs Medical Center/Sulpizio Cardiovascular Center). Patients were included if they had an AIS with cryptogenic etiology and had ICM placement between June 2017 and September 2023. Baseline demographics and ICM metrics were compared between patients that did or did not have atrial fibrillation (AF) detected with frequencies, chi-squared or t-test as appropriate. Results: A total of 134 patients were included (mean [SD]): age 69.1 years [12.5], female 40%, and median NIHSS 3 [SD 5]. AF was detected in 23.3%. Mean time to detection was 9.5 months (SD 12.8). The rate of detection was 13.5%, 18% and 21% at 6, 12, and 36 months since ICM implantation, respectively. Patients with AF were older at implantation (p=0.01) and had longer duration of monitoring (p<0.001). There was a significant difference in the number of ICM between sites (p=0.01). Males (p=0.01) and patients of white race were significantly more likely to have ICM. Despite this disparity, there was no significant difference in AF detection between sites (p=0.91), race/ethnicity (p= 0.12), or identified gender (p=0.43). Conclusions: Long-term cardiac monitoring has been shown to detect significant rates of AF, especially in cryptogenic stroke. Despite the small sample, this study found that over 20% of patients with cryptogenic stroke had AF. Examination of this population revealed disparities in implementation and placement pathways. More studies and process improvements are needed to identify and reduce disparities in this treatment-changing intervention.

Abstract WP249: Risk for Ischemic and Hemorrhagic Stroke is Increased in Veterans Exposed to Agent Orange and Those With Myeloproliferative Neoplasms

Agent Orange (AO) is a dioxin containing defoliant and carcinogen used in the Korean and Vietnam War. There is limited evidence of the association between AO exposure among Veterans and stroke. Stroke is not yet part of the list of presumptive conditions according to the Promise to Address Comprehensive Toxics (PACT) Act which provides Veterans and their survivors disability compensation for conditions arising from exposure to AO. Myeloproliferative Neoplasms (MPN) are uncommon etiologies of stroke but whether AO exposure increases incidence of stroke in MPN has not been described. Utilizing the Veterans Affairs Informatics and Computing Infrastructure (VINCI) database, a case-control study was performed from 1/1/2006 – 1/26/2023 on the Veterans from Illinois, the state most representative of the US population. ICD-9 and -10 codes identified Veterans with stroke and MPN. AO exposure was verified on the Veterans’ service duration and location. Qualitative data were compared by chi-square tests. Among 586,555 Veterans from Illinois, there were 15,455 ischemic stroke (IS), 1,593 hemorrhagic stroke (HS), 2,752 MPN, and 59,393 with AO exposure. Among MPNs, there were 237 IS (41 with AO) and 26 HS (3 with AO). IS and HS were associated with AO exposure, OR 1.34 95% CI 1.28-1.41, p<0.0001, and OR 1.20 95% CI 1.03-1.39, p=0.02, respectively. MPN is associated with IS and HS, OR 3.52, 95% CI 3.08-4.03, and OR 3.54, 95% CI 2.4-5.23, both p<0.0001, respectively. There is no significant association with AO exposure among Veterans with MPN with stroke. Among non-MPN Veterans with AO exposure, there was an earlier median age of IS and HS, 67 vs. 70 and 67 vs. 71, both p<0.0001. There was no difference in median age of stroke among MPN Veterans with or without AO exposure. There were no differences with rates of hypertension, hyperlipidemia, diabetes, smoking, heart failure, and pulmonary hypertension among MPN Veterans with stroke with and without AO exposure. In conclusion, there is an association of AO exposure with IS and HS with an earlier onset among those exposed. There is a strong association between MPN and stroke independent of AO exposure. The biologic plausibility of endothelial dysfunction and accelerated atherosclerosis from AO exposure warrants further investigation.

Abstract TP280: Monogenetic Stroke Syndrome Testing in Adults: A Single Center Experience

As access and coverage of genetic testing has increased, it is being used more commonly in adults with strokes. However, no clear guidelines exist for who should undergo genetic testing. Our retrospective review aims to provide guidance in this regard and show our experience. Genetic testing was ordered at our comprehensive stroke center between June 2022 and September 2023. Tests were ordered from GeneDx and genetic material was collected by buccal swab after consent was obtained. Most of the testing was done routinely in the outpatient setting, but was rarely performed inpatient when diagnosis would change acute management. Genetic testing was ordered for 41 patients. Tests ordered included whole exome sequencing, mitochondrial genome sequencing, Marfan syndrome and thoracic aortic aneurysm and dissection panel, Disorders of connective tissues panel and expedited whole genome sequencing. Indications for testing included evaluation of carotid and vertebral dissections, recurrent stroke, cryptogenic stroke, and leukoencephalopathy. The average age of tested patients was 47. Of these patients, 6 had not had a stroke and the testing was ordered to evaluate etiology of vertebral or carotid dissections. Of the 35 patients being evaluated for stroke etiology, 60% had at least one stroke or TIA prior to presentation. Of patients tested, 14 had evidence of dissection in the carotid arteries or vertebral arteries. At the time of analysis, 27 patients had results available, of which 15 had negative results. Positive results with pathogenic variant were seen in 4 patients. Pathologic variants detected included mutations in ABCC6, NOTCH3, MT-TL1, HBB, and MCCACHC genes. Variants of unknown significance were seen in 8 patients. These variants included mutations in MYLK, COL5A1, COL5A2, KRIT1, CCM2, XPR1, MT-CYB, MT-ND4, and MT-ATP6 genes. This study highlights that in the right clinical population, like young patients with recurrent stroke, genetic testing can be helpful to elucidate the etiology of cerebrovascular disease when standard stroke work up is inconclusive. With retrospective review, we aim to provide guidance on indications for genetic testing in adults with stroke and dissection.

Abstract WMP39: Incorporation of Automated Robotic Transcranial Doppler to Screen for Patent Foramen Ovale and Quantify Right to Left Shunt Severity in the Evaluation of Ischemic Stroke Patients for Stroke Etiology at a Comprehensive Stroke Center

Background: Patent foramen ovale (PFO) as a source of right-left shunting (RLS) is a recognized risk factor for recurrent stroke in young patients. Current standard care for RLS diagnosis includes transthoracic echocardiography (TTE), transesophageal echocardiography (TEE) and manual transcranial Doppler (TCD) which have disadvantages. The purpose of this retrospective review is to evaluate incorporation of an automated robotic TCD (rTCD) into the standard evaluation for RLS as cause of stroke, as prior studies have indicated higher sensitivity and quantification of RLS size to direct cardiology referral for potential PFO closure. Methods: Between Dec 2021-Oct 2022, 200 stroke patients age <65 were included in this retrospective review. Average age was 55.7 ± 11.1 yrs. All patients had standard TTE and an rTCD (NovaSignal) with saline bubble injection at rest and Valsalva strain for assessment of RLS performed by echo and ultrasound technicians. Neurologists read results, including RLS shunt severity using the Spencer Shunt Grading scale (0-5), where Grade 3-5 is considered large. Results: The rate of positive RLS shunt using rTCD was 55.5% (n=111), of which 23.5% (n=47) were Spencer grade 3+ or higher. No bone window rate was 8.5% (n=17), which is lower than reported manual TCD rates. There were no rTCD RLS shunt negative patients who had a positive TTE or TEE. Of patients who had positive rTCD (n=14) and TTE with bubble, only 5 TTE’s were positive (35.7% sensitivity). Of rTCD positive patients (n=23) who also had TEE with bubble, only 11 were positive (48% sensitivity). And of 15 rTCD Grade 3+ RLS, only 11 TEE with bubble were positive (73% sensitivity). Conclusion: We successfully replaced rTCD for TTE with bubble to screen for RLS on patients who were admitted with a stroke or TIA, with the following advantages. Non-TCD technicians could be trained to perform the tests with accuracy. rTCD was more sensitive in detecting RLS than TTE with bubble. Quantification of RLS severity identified stroke patients with potentially higher risk of recurrence, prioritized to more aggressive medical management and cardiology referral for TEE and potential PFO closure.

Abstract 61: The Effect of Remote Ischemic Conditioning in Stroke Subtypes: A Subgroup Analysis From the RESIST Trial

Introduction: Remote ischemic conditioning (RIC) is a simple and non-invasive procedure that has proved safe and feasible in numerous smaller clinical trials. Still, mixed results have been found in recent large randomized controlled trials. Here we present a predefined subgroup analysis of the RESIST trial on the effect of RIC in subgroups of acute ischemic stroke (AIS) and whether this effect is modified by adherence to RIC. Methods: The subgroups were defined as large artery atherosclerotic disease (LAA), small vessel disease (SVD), cardioembolic, and unknown/other/multiple/rare, and were based on ICD-10 discharge diagnoses assigned by the treating physician to define stroke etiology. Acceptable treatment adherence was defined as at least 80% received out of planned cycles. The outcome analysis used the entire range (‘shift analysis’) of the 90-day modified Rankin Scale score (ordinal logistic regression). ClinicalTrials.gov:NCT03481777. Results: A total of 902 patients were included in the target population group, 466 in the sham group, and 436 in the RIC group. RIC did not significantly improve functional outcome in adherent patients with LAA, cardioembolic or multiple/unknown etiologies. In SVD patients (n=94), with good treatment adherence, RIC treatment was associated with a significantly improved 90-day functional outcome, unadjusted OR (95% CI): 2.47 (1.01-6.02), p= 0.047. In patients with SVD, 4 patients (8%) in the RIC group compared to 0 patients in the sham group had atrial fibrillation (AF), p=0.050. The association remained significant after adjusting for AF, adjusted OR (95% CI): 2.64 (1.07-6.54), p= 0.035. Conclusions: In patients with AIS due to SVD, who had good treatment adherence, RIC treatment was associated with improved functional outcome at 90 days. These results are encouraging but should only be hypothesis-generating for future studies.

Abstract TP110: Strengthening Neurology and Cardiology Care Collaboration: Getting to the Heart of Stroke Initiative

Introduction: The American Heart Association (AHA) estimates 1 in 3 acute ischemic strokes (AIS) are cryptogenic and approximately 1 in 4 survivors will have another event. Identifying the AIS etiology will help define appropriate therapy and lower the likelihood of having another stroke. Over 67% of Black Americans have at least 1 risk factor for AIS and a higher morbidity & mortality compared to any other racial group. To address these gaps, the AHA launched Getting To The Heart Of Stroke in 2022, in conjunction with HCA Healthcare and HCA Healthcare Foundation, to improve the identification of stroke etiology by strengthening neurology & cardiology care collaboration. An overarching goal of this initiative is to improve healthcare disparities by assuring correct data collection of socioeconomic data, assessing barriers to care and addressing social determinants of health. Methods: Using a learning collaborative model, 10 HCA Comprehensive Stroke Centers, along with their clinical and administrative leadership were engaged. Monthly virtual performance improvement consultations are held to discuss actions taken, identify trends between sites, and develop PDSAs (Plan-Do-Study-Act). Their clinical multidisciplinary teams defined custom and existing metrics using Get With The Guidelines®-Stroke to measure the impact of best practice implementation. Results: Gaps include inconsistent identification of stroke etiology, lack of race documentation and lack of standardized social needs assessments. Barriers include a lack of standard triggers for cardiology and neurology consults on cryptogenic stroke and widely variable documentation by hospital. Sites are creating communication points between departments utilizing a multidisciplinary committee of stroke and cardiology team members. Conclusion: Early data suggest the need to establish standardized processes for the identification of cryptogenic stroke. A framework is necessary to build the foundational relationship between neurology & cardiology to positively impact cryptogenic stroke patient care. Over the next 2 years, the initiative will continue to explore an enhanced framework to identify cryptogenic stroke, optimize secondary prevention strategies, and ensure equitable care.

Abstract TP90: Feasibility of Robotic Exoskeleton Intervention in the Stroke Population During Acute Hospitalization

Introduction: Patients hospitalized with a stroke have limited mobility during the acute recovery phase. Those requiring significant assistance to mobilize often experience greater periods of immobility. Research in subacute rehabilitation demonstrates safe and feasible use of robotic exoskeletons for upright positioning and reciprocal motions similar to gait kinematics post stroke. This study explores the feasibility and frequency of adverse events with robotic exoskeleton during acute hospitalization post stroke. Methods: Retrospective design using the electronic health record to identify patients hospitalized with a stroke between 1/1/19 and 12/31/22. Patients that completed a single session of robotic exoskeleton in conjunction with traditional physical therapy met criteria. All participants met the manufacturer’s criteria for device use. Those who did not complete robotic intervention were excluded. Thirty-four patients were included and data obtained from physical therapy documentation of the initial session in the robotic device. Data collected included adverse events atypical of physiologic responses found with traditional physical therapy movement strategies including fracture, cardiac event, skin tear, dislocation and declining neurologic function. Further data collected includes stroke etiology, location, post stroke day intervention completed, steps taken and duration of upright weight bearing in the device. Results: Data revealed 0 patients had an adverse event with a total of 5 sessions terminated, all in patients with ischemic infarcts. Reasons for termination included orthostatic hypotension, pain in stance and fatigue. The mean step count was 106 with standard deviation (SD)of 102. The mean upright time was 19 minutes with SD of 8 minutes. Intervention was initiated on average at day 8 with SD of 7 days. Conclusion: Robotic exoskeleton is feasible during acute hospitalization with patients post stroke and yields no adverse events. Adjunct use of this device allows patients to participate in weight bearing, upright posture and neuromuscular facilitation for reciprocal motion allowing movement which otherwise may not be possible at this acute stage given the burden of mobility and level of neurologic impairment.

Exploring the associations between physical activity level, cognitive performance, and response to computerized cognitive training among chronic stroke patients

AbstractBackgroundPost‐stroke attentional and working memory deficits are common and represent relevant predictors of long‐term functional recovery and outcome. The individual responses to cognitive rehabilitation and interventions vary between patients and are influenced by multiple factors. Recently, a link between the level of engagement in physical activities and cognitive rehabilitation has been suggested. However, few previous studies have tested the predictive value of physical activity on cognitive performance and response to cognitive training among chronic stroke patients. There is also a lack of knowledge concerning the prognostic value of index stroke characteristics on physical activity in chronic phase.MethodIn this cross‐sectional and longitudinal study, including stroke survivors suffering mild‐to‐moderate strokes (n = 52, mean age = 70 years), we used Bayesian regression to test the association between cognitive performance and response to a 3‐week intervention with a commonly used computerized cognitive training (CCT) system and baseline physical activity level measured with International Physical Activity Questionnaire. We also tested the association between physical activity level in chronic phase and stroke characteristics, including stroke severity (National Institutes of Health Stroke Scale), ischemic stroke etiology (Trial of Org 10172 in Acute Stroke Treatment), and stroke location (n = 66, mean age = 68 years). For descriptive purposes, we included 104 sex‐ and age‐matched healthy controls (mean age = 69 years).ResultsThe analyses revealed anecdotal evidence of a positive association between overall cognitive performance and daily minutes of sedentary behavior, indicating that better cognitive performance was associated with more daily hours of sitting still. We found no support for an association between cognitive performance and response to CCT with activity level. In addition, the analysis showed group differences in sedentary behavior between patients with small‐vessel disease (n = 20) and cardioembolism (n = 7), indicating more sedentary behavior in patients with small‐vessel disease. There was no further support for a predictive value of index stroke characteristics on physical activity level.ConclusionThe results do not support that baseline physical activity level is a relevant predictor of the overall performance or response to CCT in this sample of chronic stroke patients. Similarly, the analyses revealed little evidence for an association between index stroke characteristics and future activity level in patients surviving mild‐to‐moderate stroke.

Abstract TP271: A Retrospective Analysis of Demographic and Clinical Variables Within a Single Center Young Stroke Cohort

Introduction: Despite significant efforts to increase public awareness of cerebrovascular disease, the incidence of stroke and transient ischemic attack (TIA) in young adults has remained elevated, representing a major public health concern. We sought to better characterize our young stroke population in order to gain insight as to where targeted interventions could be beneficial in community outreach and support of affected patients. Methods: We conducted a retrospective study evaluating young adults (under 50 years of age) presenting to a single urban academic medical center with acute ischemic stroke or TIA between 2013 and 2022. Demographic information and clinical variables (including past medical history, Trial of Org 10172 in Acute Stroke Treatment [TOAST] classification of stroke etiology, and discharge disposition) were extracted from the electronic medical record and descriptive statistics were calculated. Results: A total of 408 patients were reviewed. Within this study population, the median age was 43 years (IQR 38-47 years) and 235 (57.6%) were men. The median initial National Institutes of Health Stroke Scale upon presentation was 3 (IQR 1-7). The most common stroke risk factors were tobacco use (44.6%), pre-existing cardiovascular disease (26.2%), and other substance use (23.8%). The most common TOAST classification upon discharge was Stroke of Undetermined Etiology (32.9%). Most patients (244, 59.8%) were discharged directly to home from the hospital, although 140 (34.3%) were transitioned to another facility, including acute rehabilitation facilities (95, 23.3%), skilled nursing facilities (22, 5.4%), and long-term acute care hospitals (11, 2.7%). Conclusion: Our study highlights that the continued high incidence of stroke in the young may be at least partially attributable to a high prevalence of traditional cardiovascular risk factors, thus emphasizing the importance of smoking cessation counseling and early treatment of hypertension in the primary care setting. In addition, while most young patients will present with minor stroke symptoms, a significant portion are unable to return directly to home upon discharge from the hospital.

Association of covert brain infarct phenotype with stroke recurrence in first-ever manifest ischemic stroke according to etiology.

Covert brain infarcts (CBI) are frequent incidental findings on MRI and associated with future stroke risk in patients without a history of clinically evident cerebrovascular events. However, the prognostic value of CBI in first-ever ischemic stroke patients is unclear and previous studies did not report on different etiological stroke subtypes. We aimed to test CBI phenotypes and their association with stroke recurrence in first-ever ischemic stroke patients according to stroke etiology. This study is a pooled data analysis of two prospectively collected cohorts of consecutive first-ever ischemic stroke patients admitted to the comprehensive stroke centers of Bern (Switzerland) and Graz (Austria). CBI phenotypes were identified on brain MRI within 72 h after admission. All patients underwent a routine follow-up (median: 12 months) to identify stroke recurrence. Of 1577 consecutive ischemic stroke patients (median age: 71 years), 691 patients showed CBI on brain MRI (44%) and 88 patients had a recurrent ischemic stroke (6%). Baseline CBI were associated with stroke recurrence in multivariable analysis (HR 1.9, 95% CI 1.1-3.3). CBI phenotypes with the highest risk for stroke recurrence were cavitatory CBI in small vessel disease (SVD)-related stroke (HR 7.1, 95% CI 1.6-12.6) and cortical CBI in patients with atrial fibrillation (HR 3.0, 95% CI 1.1-8.1). This study reports a ≈ 2-fold increased risk for stroke recurrence in first-ever ischemic stroke patients with CBI. The risk of recurrent stroke was highest in patients with cavitatory CBI in SVD-related stroke and cortical CBI in patients with atrial fibrillation.Subject terms: Covert brain infarcts, stroke.

First-ever acute ischemic strokes in HIV-infected persons: A case-control study from stroke units.

The stroke risk for persons living with human immunodeficiency virus (PLHIVs) doubled compared to uninfected individuals. Stroke-unit (SU)-access, acute reperfusion therapy-use and outcome data on PLHIVs admitted for acute ischemic stroke (AIS) are scarce. AIS patients admitted (01 January 2017 to 31 January 2021) to 10 representative Paris-area SUs were screened retrospectively from the National Hospitalization Database. PLHIVs were compared to age-, initial NIHSS- and sex-matched HIV-uninfected controls (HUCs). Outcome was the 90-day modified Rankin Scale score. Among 126 PLHIVs with confirmed first-ever AIS, ~80% were admitted outside the thrombolysis-administration window. Despite antiretrovirals, uncontrolled plasma HIV loads exceeded 50 copies/mL (26% of all PLHIVs; 38% of those ≤55 years). PLHIVs' stroke causes by decreasing frequency were large artery atherosclerosis (LAA), undetermined, other cause, cerebral small-vessel disease (CSVD) or cardioembolism. No stroke etiology was associated with HIV duration or detectable HIVemia. MRI revealed previously unknown AIS in one in three PLHIVs, twice the HUC rate (p = 0.006). Neither group had optimally controlled modifiable cardiovascular risk factors (CVRFs): 20%-30% without specific hypertension, diabetes, and/or dyslipidemia treatments. Their stroke outcomes were comparable. Multivariable analyses retained good prognosis associated solely with initial NIHSS or reperfusion therapy. Older age and hypertension were associated with CSVD/LAA for all PLHIVs. Standard neurovascular care and reperfusion therapy were well-tolerated. The high uncontrolled HIV-infection rate and suboptimal CVRF treatment support heightened vigilance to counter suboptimal HIV suppression and antiretroviral adherence, and improve CVRF prevention, mainly for younger PLHIVs. Those preventive, routine measures could lower PLHIVs' AIS risk.

Discordance between LDL-C and apolipoprotein B is associated with large-artery-atherosclerosis ischemic stroke in patients ⩽70 years of age.

Low density lipoprotein (LDL-C) and other atherogenic lipoproteins are coated by apolipoprotein B100 (apoB). The correlation between LDL-C and apoB is usually thight, but in some cases LDL-C underestimates apoB levels and residual cardiovascular risk. We aimed to assess if a discordance of LDL-C-levels with apoB levels is associated with LAA stroke. We included patients with an acute ischemic stroke from two prospective studies enrolled at the University Hospital Bern, Basel and Zurich, Switzerland. LDL-C and apoB were measured within 24 h of symptom onset. By linear regression, for each LDL-C, we computed the expected apoB level assuming a perfect correlation. Higher-than-expected apoB was defined as apoB level being in the upper residual tertile. Overall, we included 1783 patients, of which 260 had a LAA stroke (15%). In the overall cohort, higher-than-expected apoB values were not associated with LAA. However, a significant interaction with age was present. Among the 738 patients ⩽70 years of age, a higher-than-expected apoB was more frequent in patients with LAA- versus non LAA-stroke (48% vs 36%, p = 0.02). In multivariate analysis, a higher-than-expected apoB was associated with LAA stroke (aOR = aOR 2.48, 95%CI 1.14-5.38). Among those aged ⩽70 years and with LAA, 11.7% had higher than guideline-recommended apoB despite LDL-C ⩽ 1.8 mmol/L (<70 mg/dl), compared to 5.9% among patients with other stroke etiologies (p = 0.04). A triglyceride cut-off of ⩾0.95 mmol/L had, in external validation, a sensitivity of 71% and specificity of 52% for apoB ⩾ 0.65 g/L among patients with LDL-C <1.8 mmol/L. Among patients aged ⩽70 years, a higher-than-expected apoB was independently associated with LAA stroke. Measuring apoB may help identify younger stroke patients potentially benefiting from intensified lipid-lowering therapy.

Prevalence of Fabry disease and GLA variants in young patients with acute stroke: The challenge to widen the screening. The Fabry-Stroke Italian Registry

BackgroundFabry disease (FD) is a treatable X-linked lysosomal storage disorder caused by GLA gene variants leading to alpha-galactosidase A deficiency. FD is a rare cause of stroke, and it is still controversial whether in stroke patients FD should be searched from the beginning or at the end of the diagnostic workup (in cryptogenic strokes). MethodsFabry-Stroke Italian Registry is a prospective, multicentric screening involving 33 stroke units. FD was sought by measuring α-galactosidase A activity (males) and by genetic tests (males with reduced enzyme activity and females) in patients aged 18–60 years hospitalized for TIA, ischemic stroke, or intracerebral hemorrhage. We diagnosed FD in patients with 1) already known pathogenic GLA variants; 2) novel GLA variants if additional clinical, laboratory, or family-derived criteria were present. ResultsOut of 1906 patients, we found a GLA variant in 15 (0.79%; 95%CI 0.44–1.29) with a certain FD diagnosis in 3 (0.16%; 95%CI 0.03–0.46) patients, none of whom had hemorrhage. We identified 1 novel pathogenic GLA variant. Ischemic stroke etiologies in carriers of GLA variants were: cardioaortic embolism (33%), small artery occlusion (27%), other causes (20%), and undetermined (20%). Mild severity, recurrence, previous TIA, acroparesthesias, hearing loss, and small artery occlusion were predictors of GLA variant. ConclusionIn this large multicenter cohort the frequency of FD and GLA variants was consistent with previous reports. Limiting the screening for GLA variants to patients with cryptogenic stroke may miss up to 80% of diagnoses. Some easily recognizable clinical features could help select patients for FD screening.

Embolic stroke of undetermined source: Focusing on atrial cardiopathy and patent foramen ovale

BackgroundAtrial cardiopathy(AC) and patent foramen ovale (PFO) are two etiologies of embolic strokes of undetermined source (ESUS). We aimed to explore the relationship between them in ESUS. MethodsA total of 1146 participants were included from January 2019 to June 2022, which included the ESUS group and non-embolic stroke which includes LAA(large arterial atherosclerosis) + SAO(small artery occlusion) group. AC was defined as the presence of at least one of the following: PTFV1(P-wave terminal force in lead V1) > 4000 μV*ms in the electrocardiograms, NT-proBNP(N-terminal probrain natriuretic peptide) > 250 pg/mL in laboratory tests or LAD(left atrial diameter) > 3.8 cm for women and > 4.0 cm for men in cardiac ultrasound. The presence of PFO was assessed by transthoracic echocardiography, transcranial Doppler ultrasound, transesophageal echocardiography or cardiac MRI. PFO was considered pathogenic if the RoPE score was 7 to 10. ResultsThe prevalence of AC and PFO was higher in the ESUS group than the LAA + SAO group. The prevalence of AC was lower in ESUS patients with pathogenic PFO (37.9%) than those without PFO (68.4%) and with incidental PFO (64.0%) (p = 0.006). The prevalence of pathogenic PFO was lower in ESUS patients with AC than those without AC (6.0% vs. 17.8%, p = 0.006). The AUC(area under the curve) of PTFV1 for predicting ESUS was 0.724 [95%CI (0.686–0.762), p < 0.05)], indicating that PTFV1 the most valuable AC biomarker. ConclusionsThe prevalence of AC is inversely related to the prevalence of pathogenic PFO in ESUS patients. PTFV1 was the most valuable index to predict ESUS among the AC biomarkers.

Cerebral small vessel disease and stroke: Linked by stroke aetiology, but not stroke lesion location or size

BackgroundCerebral small vessel disease (SVD) has previously been associated with worse stroke outcome, vascular dementia, and specific post-stroke cognitive deficits. The underlying causal mechanisms of these associations are not yet fully understood. We investigated whether a relationship between SVD and certain stroke aetiologies or a specific stroke lesion anatomy provides a potential explanation. MethodsIn a retrospective observational study, we examined 859 patients with first-ever, non-SVD anterior circulation ischemic stroke (age = 69.0±15.2). We evaluated MRI imaging markers to assess an SVD burden score and mapped stroke lesions on diffusion-weighted MRI. We investigated the association of SVD burden with i) stroke aetiology, and ii) lesion anatomy using topographical statistical mapping. ResultsWith increasing SVD burden, stroke of cardioembolic aetiology was more frequent (ρ = 0.175; 95 %-CI = 0.103;0.244), whereas cervical artery dissection (ρ = -0.143; 95 %-CI = -0.198;-0.087) and a patent foramen ovale (ρ = -0.165; 95 %-CI = -0.220;-0.104) were less frequent stroke etiologies. However, no significant associations between SVD burden and stroke aetiology remained after additionally controlling for age (all p>0.125). Lesion-symptom-mapping and Bayesian statistics showed that SVD burden was not associated with a specific stroke lesion anatomy or size. ConclusionsIn patients with a high burden of SVD, non-SVD stroke is more likely to be caused by cardioembolic aetiology. The common risk factor of advanced age may link both pathologies and explain some of the existing associations between SVD and stroke. The SVD burden is not related to a specific stroke lesion location.

Left atrial reservoir strain is a superior discriminator of cardioembolism in ischaemic stroke.

Echocardiographic measures of left heart size and function have long been associated with cardioembolic mechanisms of stroke development, however, the diagnostic performance and comparison of measures of atrial function in this context has not been well studied. We sought to evaluate the diagnostic performance of left atrial reservoir strain (LASr) in identification of cardioembolism in the ischaemic stroke population relative to traditional measures of left heart size and function. Consecutive patients admitted to our institution with ischaemic stroke or transient ischaemic attack were recruited and underwent comprehensive transthoracic echocardiography. Strokes were classified by aetiology with comparison undertaken between cardioembolic and non-cardioembolic types. Four hundred and eighteen consecutive stroke patients with a cardioembolic (n = 229) or non-cardioembolic (n = 189) stroke aetiology were analysed. LASr was impaired in cardioembolic compared with non-cardioembolic strokes (16.7 ± 8.2% vs. 26.0 ± 5.5%, P < 0.01) and provided greatest discrimination [area under the curve (AUC) 0.813, 95%CI 0.773-0.858] in differentiating stroke subtypes when compared with LVEF (AUC difference 0.150, P < 0.01), LAVI (AUC difference 0.083, P < 0.01), and E/e' (AUC difference 0.163, P < 0.01). Inclusion of LASr in a model with conventional left heart echocardiographic factors improved model performance with a net reclassification improvement of 1.083 (95%CI 0.945-1.220, P < 0.01). Further, a proposed user-defined model-based clinical algorithm with LASr demonstrated improved diagnostic accuracy of the identification of cardioembolic stroke subtypes which was best appreciated in patients without atrial fibrillation. LASr may provide enhanced diagnostic accuracy beyond conventional echocardiographic measures to discriminate cardioembolic from non-cardioembolic stroke mechanisms, in particular amongst those without comorbid atrial fibrillation.

Etiology and Risk Factors for Strokes in the Pediatric Population

Pediatric arterial ischemic stroke (AIS) and hemorrhagic stroke represent a relatively uncommon yet significant source of neurological challenges for neonates and children, resulting in outcomes such as hemiparesis, intellectual disabilities, and epilepsy. The etiology of pediatric strokes differs from the typical causes seen in adult stroke cases. Therefore, understanding the specific risk factors associated with strokes in children is crucial for facilitating early diagnosis, which regrettably remains frequently delayed. AIS incidence varies due to factors such as patient age, types of cerebral vascular diseases, other chronic conditions and geographic location. In this comprehensive review, we delve into the epidemiology, clinical manifestation and risk factors linked to arterial ischemic stroke and hemorrhagic stroke in neonates and children.

An interpretable machine learning model for stroke recurrence in patients with symptomatic intracranial atherosclerotic arterial stenosis.

Symptomatic intracranial atherosclerotic stenosis (SICAS) is the most common etiology of ischemic stroke and one of the main causes of high stroke recurrence. The recurrence of stroke is closely related to the prognosis of ischemic stroke. This study aims to develop a machine learning model based on high-resolution vessel wall imaging (HR-VWI) to predict the risk of stroke recurrence in SICAS. This study retrospectively collected data from 180 SICAS stroke patients treated at the hospital between 2020.01 and 2022.01. Relevant imaging and clinical data were collected, and follow-up was conducted. The dataset was divided into a training set and a validation set in a ratio of 7:3. We employed the least absolute shrinkage and selection operator (LASSO) regression to perform a selection on the baseline data, laboratory tests, and neuroimaging data generated by HR-VWI scans collected from the training set. Finally, five machine learning techniques, including logistic regression model (LR), support vector machine (SVM), Gaussian naive Bayes (GNB), Complement naive Bayes (CNB), and k-nearest neighbors algorithm (kNN), were employed to develop a predictive model for stroke recurrence. Shapley Additive Explanation (SHAP) was used to provide visualization and interpretation for each patient. The model's effectiveness was evaluated using average accuracy, sensitivity, specificity, precision, f1 score, PR curve, calibration curve, and decision curve analysis. LASSO analysis revealed that "history of hypertension," "homocysteine level," "NWI value," "stenosis rate," "intracranial hemorrhage," "positive remodeling," and "enhancement grade" were independent risk factors for stroke recurrence in SICAS patients. In 10-fold cross-validation, the area under the curve (AUC) ranged from 0.813 to 0.912 in ROC curve analysis. The area under the precision-recall curve (AUPRC) ranged from 0.655 to 0.833, with the Gaussian Naive Bayes (GNB) model exhibiting the best ability to predict stroke recurrence in SICAS. SHAP analysis provided interpretability for the machine learning model and revealed essential factors related to the risk of stroke recurrence in SICAS. A precise machine learning-based prediction model for stroke recurrence in SICAS has been established to assist clinical practitioners in making clinical decisions and implementing personalized treatment measures.

Effects of elevated remnant cholesterol on outcomes of acute ischemic stroke patients receiving mechanical thrombectomy.

Large cohort studies provided evidence that elevated remnant cholesterol (RC) was an important risk factor for ischemic stroke. However, the association between high RC and clinical outcomes in acute ischemic stroke (AIS) individuals was still undetermined. This retrospective study enrolled 165 AIS patients undergoing mechanical thrombectomy in one tertiary stroke center. We divided patients into two groups based on the median of their RC levels (0.49 mmol/L). The modified Rankin Scale (mRS) was used to evaluate the primary outcome 90 days after the onset of symptoms. The mRS scores ≤ 2 and ≤ 1 at 90 days were deemed as favorable and excellent outcomes, respectively. In the overall AIS patients undergoing mechanical thrombectomy, there was no obvious distinction between the high and low RC group at 90-day favorable outcome (41.0% vs. 47.1%, P = 0.431) or excellent outcome (23.1% vs. 31.0%, P = 0.252). In the subgroup analysis stratified by stroke etiology, non-large artery atherosclerosis (non-LAA) stroke patients yielded with less favorable or excellent prognosis in the high RC group (26.8% vs. 46.8%, adjusted OR = 0.31, 95%CI: 0.11-0.85, P = 0.023; or 12.2% vs. 29.0%, adjusted OR = 0.18, 95%CI: 0.04-0.80, P = 0.024, respectively.). Post hoc power analyses indicated that the power was sufficient for favorable outcome (80.38%) and excellent outcome (88.72%) in non-LAA stroke patients. Additionally, RC can enhance the risk prediction value of a poor outcome (mRS scores 3-6) based on traditional risk indicators (including age, initial NIHSS score, operative duration, and neutrophil-to-lymphocyte ratio) for non-LAA stroke patients (AUC = 0.86, 95%CI: 0.79-0.94, P < 0.001). In AIS patients undergoing mechanical thrombectomy, elevated RC was independently related to poor outcome for non-LAA stroke patients, but not to short-term prognosis of LAA stroke patients.