Cryptogenic Ischemic Stroke Research Articles

P3709Risk of recurrent cerebral ischemia in young patients with cryptogenic ischemic stroke and patent foramen ovale

Abstract Background The cause of ischemic stroke (IS) remains often unclear in young patients. Relevant structural heart abnormities with known embolic potential may represent cause of IS also in young population. A persistent foramen ovale (PFO) is a known risk factor for paradoxical embolism, including ischemic stroke (IS). Aims The aims of our prospective study were to assess the rates of recurrent ischemic stroke events in young IS patients with PFO during a 35-month follow-up period (FUP) on effective antiplatelet therapy (OAT) and to evaluate a potential relationship with the presence of PFO on transesophageal echocardiography (TEE). Methods The study set consisted of young acute IS patients <50 years enrolled in the prospective HISTORY (Heart and Ischemic STrOke Relationship studY) study, NCT01541163). In all patients, the brain ischemia was confirmed on CT or MRI. Admission ECG, serum specific cardiac markers, transesophageal echocardiography, 24-hour and 3-week ECG-Holter were performed in all patients. Results Out of 980 patients enrolled in the HISTORY study, 260 patients were younger than 50 years and 185 (56% males, mean age 41±8 years) patients were classified as cryptogenic IS in ASCOD classification. PFO was diagnosed in 60 patients (32%). Six new clinically apparent recurrent ischemic brain events were recorded during a 35-month FUP. No significant difference was found in the presence of IS recurrence between patient group with PFO and without PFO (2 [3.2% patients with PFO] versus 4 [3.2% without PFO] of young IS patients, P=0.99). Conclusion The presence of PFO was not associated with a higher risk of new brain ischemic lesions in young patients with with cryptogenic ischemic stroke during a 35-month follow-up period. Number of recurrent clinical IS is relatively small, thus achieved results may be not so robust. Acknowledgement/Funding Grant support IGA MZ CR NT/14288-3, AZV MZ CR 17-30101A, IGA LF UP Olomouc (2016-2018), FNOL SUG No. 87-85

Risk of recurrent ischemic stroke in young cryptogenic patients with embolic stroke of undetermined source

In young patients, cause of ischemic stroke (IS) remains very often cryptogenic and thus effectiveness of secondary prevention may be uncertain. Elderly cryptogenic IS patients (CIS) with ESUS (Embolic Stroke of Undetermined Source) have a higher risk of recurrent IS (RIS). The aim was to compare risk of RIS between ESUS and other young CIS patients. The study set consisted of young acute IS patients < 50 years enrolled in the prospective HISTORY (Heart and Ischemic STrOke Relationship studY) study registered on ClinicalTrials.gov (NCT01541163). In all patients, brain ischemia was confirmed on CT/MRI. Admission ECG, serum specific cardiac and thrombophilia markers, neurosonology, TEE, 24-hour and 3-week ECG-Holter were performed to assess cause of IS according to the ASCOD classification. Of 279 enrolled patients < 50 years (153 males, mean age 41.1 ± 7.8 years), 199 (71%) were identified as cryptogenic and 106 (59 males, mean age 40.7 ± 7.5 years) fulfilled ESUS criteria. During the follow-up with a median of 17 months, two (2%) ESUS and 4 (4%) other CIS patients suffered from RIS (p=0.421). The mean time to RIS did not differ between both groups (14 vs. 27 months, p=0.248). One-year risk of RIS was 0 for ESUS and 0.025 (95% CI: 0-0.059) for other CIS patients (p=0.248). Conclusion: The risk of RIS was very low and did not differ between young ESUS and other CIS patients. Supported by the grant of Ministry of Health of Czech Republic n. 17-30101A and IGA LF UP_008_2019.

Carotid Webs in Cryptogenic Ischemic Strokes: A Matched Case-Control Study

Background: Young individuals with symptomatic carotid webs may be predisposed to ischemic strokes. However, evidence remains scarce. This investigation reports the frequency of carotid webs among patients with cryptogenic strokes compared to a control group. Methods: Consecutive cryptogenic ischemic strokes and trauma patients were identified. Additional inclusion criteria required age 18-60 years and availability of head/neck computed tomography (CT) angiography. CT angiogram (CTA) neck images were evaluated independently by 2 fellowshiptrained specialists. A carotid web was defined by a shelf-like, linear filling defect in the posterior internal carotid artery bulb. Results: Of 1877 patients presenting with ischemic strokes in 2015-2017, 165 were diagnosed with cryptogenic strokes, 51 of whom met the inclusion criteria of age and CTA availability. Fifty one trauma cases were matched for age and sex. After imaging analysis, 13 carotid webs (25%) were identified in the 51 cryptogenic stroke group versus 0 (0%; P < .001) in trauma subjects. Thirty-nine of the 51 cryptogenic ischemic stroke patients were found with carotid anterior distribution infarcts, of which 9 (23%) were found with ipsilateral carotid webs. There were more proximal large vessel occlusions in the cryptogenic patients with carotid webs, compared to those without (P = .04). All carotid webs led to less than 30% degree of stenosis. Conclusions: Carotid webs were found at a significantly higher frequency in patients with cryptogenic ischemic strokes compared to controls, indicating a potentially thrombogenic nature of these lesions in young patients. Additionally, intracranial large vessel occlusions were more common in patients with symptomatic carotid webs, presenting with ipsilateral strokes.

Prolonged Cardiac Rhythm Monitoring and Secondary Stroke Prevention in Patients With Cryptogenic Cerebral Ischemia.

Background and Purpose- Although prolonged cardiac rhythm monitoring (PCM) can reveal a substantial proportion of ischemic stroke (IS) patients with atrial fibrillation not detected by conventional short-term monitoring, current guidelines indicate an uncertain clinical benefit for PCM. We evaluated the impact of PCM on secondary stroke prevention using data from available to date randomized clinical trials and observational studies. Methods- We performed a comprehensive literature search in MEDLINE, SCOPUS, CENTRAL (Cochrane Central Register of Controlled Trial), and conference proceedings to identify studies reporting stroke recurrence rates in patients with history of cryptogenic IS or transient ischemic attack (TIA) receiving PCM compared with patients receiving conventional (non-PCM) cardiac monitoring. Results- We included 4 studies (2 randomized clinical trials and 2 observational studies), including a total of 1102 patients (mean age: 68 years, 41% women). We documented an increased incidence of atrial fibrillation detection (risk ratio=2.46; 95% CI, 1.61-3.76) and anticoagulant initiation (risk ratio=2.07; 95% CI, 1.36-3.17) and decreased risk of recurrent stroke (risk ratio=0.45; 95% CI, 0.21-0.97) and recurrent stroke/TIA (risk ratio=0.49; 95% CI, 0.30-0.81) during follow-up for IS/TIA patients who underwent PCM compared with IS/TIA patients receiving conventional cardiac monitoring. In the subgroup analysis, according to study type, atrial fibrillation detection, anticoagulant initiation, and IS/TIA recurrence rates were comparable between PCM and non-PCM in randomized clinical trials and observational studies. No evidence of heterogeneity (I2<12%) was documented across all the aforementioned subgroups. Conclusions- We provide preliminary evidence for a potential impact of PCM on secondary stroke prevention, as patients with cryptogenic IS/TIA undergoing PCM had higher rates of atrial fibrillation detection, anticoagulant initiation, and lower stroke recurrence.

Predictors of Recurrent Ischemic Stroke in Patients with Embolic Strokes of Undetermined Source and Effects of Rivaroxaban Versus Aspirin According to Risk Status: The NAVIGATE ESUS Trial

Background: Embolic stroke of undetermined source (ESUS) identifies patients with cryptogenic ischemic stroke presumed due to embolism from several unidentified sources. Among patients with recent ESUS, we sought to determine independent predictors of recurrent ischemic stroke during treatment with aspirin or rivaroxaban and to assess the relative effects of these treatments according to risk. Methods: Exploratory analyses of 7213 participants in the NAVIGATE ESUS international trial who were randomized to aspirin 100 mg/day or rivaroxaban 15 mg/day and followed for a median of 11 months, during which time there were 309 first recurrent ischemic strokes (4.6% per year). Baseline features were correlated with recurrent stroke by multivariate analysis. Results: The 7 independent predictors of recurrent stroke were stroke or transient ischemic attack (TIA) prior to the qualifying stroke (hazard ratio [HR] 2.03 95% confidence internal [CI] 1.58-2.60), current tobacco user (HR 1.62, 95% CI 1.24-2.12), age (HR 1.02 per year increase, 95%CI 1.01-1.03), diabetes (HR 1.28, 95% CI 1.01-1.64), multiple acute infarcts on neuroimaging (HR 1.49, 95% CI 1.09-2.02), aspirin use prior to qualifying stroke (HR 1.34, 95% CI 1.02-1.70), and time from qualifying stroke to randomization (HR .98, 95% CI .97-.99). The rate of recurrent stroke rate was 2.6% per year for participants without any of these risk factors, and increased by an average of 45% for each independent predictor (P < .001). There were no significant interactions between treatment effects and independent stroke predictors or stroke risk status. Conclusions: In this large cohort of ESUS patients, several features including prior stroke or TIA, advanced age, current tobacco user, multiple acute infarcts on neuroimaging, and diabetes independently identified those with an increased risk of ischemic stroke recurrence. The relative effects of rivaroxaban and aspirin were similar across the spectrum of independent stroke predictors and recurrent stroke risk status.

Embolic stroke of undetermined source (ESUS) : How much monitoring is necessary?

The clinical construct of embolic stroke of unknown source (ESUS) was first described in 2014. It is defined as cryptogenic ischemic stroke after the exclusion of a lacunar infarct, a significant (≥50%) stenosis of extracranial or intracranial arteries and a cardiac source of embolism. Initially, there was hope that these patients would benefit from anticoagulation. This was based on the suspicion that imaging criteria of stroke mimic features of embolism from cardiac sources or the great arteries. In two large randomized trials with 12,600 patients neither rivaroxaban nor dabigatran could reduce the risk of recurrent stroke. Based on these results, current research is focused on paroxysmal atrial fibrillation as apotential cause of stroke in these patients. Several randomized trials could show that by prolongation of monitoring to 30days atrial fibrillation can be detected in approximately 10% of the patients. Using continuous monitoring (e. g. by implantable loop recorders) atrial fibrillation can even be detected in one quarter of the patients. Not all stroke patients can receive such an intensive monitoring. Therefore, this article summarizes the evidence and presents the resulting recommendations for patient selection and staged rhythm diagnostics and discusses arecently presented algorithm of an expert group for use in daily clinical practice.

Transthoracic echocardiography in the assessment of cardiogenic causes of ischaemic stroke.

One of the leading causes of death in Poland is stroke. Cardiogenic stroke is known to be one of the most important reasons for acute ischaemic stroke (AIS), comprising 25-30% of all AISs. Assessment of the prevalence of different risk factors of cardiogenic causes of AIS using transthoracic echocardiography (TTE). Transthoracic echocardiograms performed in patients with AIS admitted to a single neurological ward between October 2013 and September 2017 were analysed. Patients were assigned, based on the results of their TTE and their previous medical history of atrial fibrillation (AF), to one of three groups depending on the level of the risk of occurrence of cardiogenic causes of AIS. According to Dz.U.2001, no. 126, 1381 no ethical permission was needed. 663 patients with AIS were included in the study. Patients with high risk of cardiogenic cause of AIS: 26.7% (N = 177 patients [p]). Of these, 64.4% (114 p) were diagnosed with AF. 31.6% (56 p) with sinus rhythm during hospitalisation had a history of paroxysmal AF (PAF). In 11.9% (21 p) of the patients qualified to the high risk group, factors other than AF were found. Patients with moderate risk of cardiogenic cause of AIS: 10.1% (67 p). Patients with low risk of cardiogenic cause of AIS: 25.9% (172 p). Echocardiographic results led to a change in therapy in 1.21% of cases. 1. Transthoracic echocardiography performed routinely in all AIS patients affects the treatment in a very low percentage of cases. 2. The group that could benefit the most from TTE examination includes people without established indications for chronic anticoagulant therapy, in particular patients after myocardial infarction and people with additional clinical symptoms. 3. In patients with AIS, the diagnostic sensitivity of TTE in the detection of PFO is low. Young people with a cryptogenic ischaemic stroke should undergo a transoesophageal assessment.

Utility of D-dimer for oncologic disease suspicion in patients with cryptogenic ischemic stroke. (P2.3-033)

Utility of D-dimer for oncologic disease suspicion in patients with cryptogenic ischemic stroke. (P2.3-033)

Incidence, characteristics and outcomes in patients with embolic stroke of undetermined source: A population-based study

Embolic stroke of undetermined source (ESUS) represents a subgroup of cryptogenic ischemic stroke (CS) distinguished by high probability of an underlying embolic mechanism. There are scarce population-based data regarding the incidence, characteristics and outcomes of ESUS. Consecutive patients included with first-ever ischemic stroke of undetermined cause in the previously published population-based Evros Stroke Registry were further subdivided into ESUS and non-ESUS CS. Crude and adjusted [according to the European Standard Population (ESP), WHO and Segi population] incidence rates (IR) for ESUS and non-ESUS CS were calculated. Baseline characteristics, admission stroke severity (assessed using NIHSS-score), stroke recurrence and functional outcomes [determined by modified Rankin Scale (mRS) scores], were recorded during the 1-year follow-up period. We identified 21 and 242 cases with ESUS (8% of CS) and non-ESUS CS. The crude and ESP-adjusted IR for ESUS were 17.5 (95%CI: 10–25) and 16.6 (95%CI: 10–24) per 100,000 person-years. Patients with ESUS were younger (p < .001) and had lower median admission NIHSS-scores (p < .001). Functional outcomes were more favorable in ESUS at 28, 90 and 365 days. ESUS was independently (p = .033) associated with lower admission NIHSS-scores (unstandardized linear regression coefficient: -13.34;95%CI: -23.34, −3.35) on multiple linear regression models. ESUS was not related to 1-year stroke recurrence, mortality and functional improvement on multivariable analyses. In conclusion we found that ESUS cases represented 8% of CS patients in this population-based study. Despite the fact that ESUS was independently related to lower admission stroke severity, there was no association of ESUS with long-term outcomes.

Cryptogenic stroke and patent foramen ovale (abridged and translated version)

Interventional patent foramen ovale (PFO) closure should be performed in patients aged 16 to 60 years (after extensive neurological and cardiological diagnostic work-up) with a history of cryptogenic ischaemic stroke and patent foramen ovale, with moderate or extensive right-to-left shunt.In patients with cryptogenic ischaemic stroke and patent foramen ovale, who reject a PFO closure, there is no evidence of superiority of oral anticoagulation over antiplatelet therapy. Therefore, secondary prevention should be performed with aspirin or clopidogrel.Atrial fibrillation, pericardial tamponade, and pulmonary embolism are reported complications during and after implantation of an occluder. However, these events are so rare that they should not influence the recommendation for implantation.This article is an abridged and translated version of the guideline published in Nervenarzt: Diener, HC., für die Deutsche Gesellschaft für Neurologie (DGN), Grau, A.J. et al. Nervenarzt (2018) 89: 1143. https://doi.org/10.1007/s00115-018-0609-y.

Abstract TP199: Incidence, Characteristics and Outcomes in Patients With Embolic Stroke of Undetermined Source: A Population-based Study

Introduction: Embolic stroke of undetermined source (ESUS) represents a subgroup of cryptogenic ischemic stroke (CS) distinguished by high probability of an underlying embolic mechanism. There are scarce population-based data regarding the incidence, characteristics and outcomes of ESUS. Methods: Consecutive patients included with first-ever ischemic stroke of undetermined cause in the previously published population-based Evros Stroke Registry were further subdivided into ESUS and non-ESUS CS. Crude and adjusted [according to the European Standard Population (ESP), WHO and Segi population] incidence rates (IR) for ESUS and non-ESUS CS were calculated. Baseline characteristics, admission stroke severity (assessed using NIHSS-score), stroke recurrence and functional outcomes [determined by modified Rankin Scale (mRS) scores], were recorded during the 1-year follow-up period. Results: We identified 21 and 242 cases with ESUS (8% of CS) and non-ESUS CS. The crude and ESP-adjusted IR for ESUS were 17.5 (95%CI: 10-25) and 16.6 (95%CI: 10-24) per 100,000 person-years. Patients with ESUS were younger [median age 68 years (IQR:61-75) vs. 79 years (IQR:73-83); p&lt;0.001] and had lower median admission NIHSS-scores [4 points (IQR:2-8) vs. 8 points (IQR:5-16); p&lt;0.001]. Functional outcomes were more favorable in ESUS at 28 [median mRS-score: 2 (IQR:1-3) vs. 4 (IQR:3-6)], 90 [median mRS-score: 1 (IQR:0-2) vs. 4 (IQR:2-6)] and 365 days [median mRS-score: 1 (IQR:0-2) vs. 5 (IQR:2-6)]. ESUS was independently (p=0.033) associated with lower admission NIHSS-scores (unstandardized linear regression coefficient: -13.34;95%CI: -23.34, -3.35) on multiple linear regression models. ESUS was not related to 1-year stroke recurrence (HR: 0.22, 95%CI: 0.01-4.06), mortality (HR: 0.25, 95%CI: 0.02-4.36) and functional improvement (1-point shift in mRS-scores; cOR: 1.47, 95%CI: 0.59-3.70) on multivariable analyses. Conclusions: ESUS cases represented 8% of CS patients in this population-based study. Despite the fact that ESUS was independently related to lower admission stroke severity, there was no association of ESUS with long-term outcomes.

Abstract WP267: Lower Left Ventricular Longitudinal Contraction is Associated With Early-onset Cryptogenic Ischemic Stroke

Introduction: At least one third of ischemic strokes at a young age (&lt;50 years) remain cryptogenic after complete diagnostic work-up. We hypothesized that based on their neuroimaging presentation majority of these strokes may originate from the heart and that advanced cardiac ultrasound imaging might reveal hints from underlying left ventricular pathology. Methods: We prospectively recruited 26 patients aged 18-49 with cryptogenic ischemic stroke and 26 age- and sex-matched stroke-free controls. We examined all participants with transthoracic echocardiography and analyzed the left ventricular (LV) ejection fraction (LVEF) with 3-dimensional volumetry. We used speckle-tracking imaging in three planes (apical 4-chamber, 3-chamber and 2-chamber views), to determine LV global longitudinal strain (GLS), and only patients with visibility allowing analysis of all 18 LV segments were included. Tissue Doppler velocity imaging was used to determine the mitral annular plane systolic excursion (MAPSE), as a mean of six annular points in the 3 apical planes. Measurements were normally distributed and group-level differences were analyzed by paired-samples T-tests. Results: A total of 26 pairs had adequate visibility to examine LVEF, 20 to assess GLS, and 25 to examine MAPSE. There was no significant difference in LV ejection fraction between patients and controls (mean 59.0 vs 61.4 (%); P=0.300). LV global longitudinal strain was significantly lower in patients compared with controls (mean 18.0 vs 19.9 (%); P=0.012). Furthermore, MAPSE was lower in patients (mean 13.3 vs 14.2(mm); P=0.044). Conclusion: Young patients with cryptogenic ischemic stroke had lower longitudinal LV contraction than stroke-free individuals of the same age—without differences in LVEF—suggesting that subclinical LV systolic dysfunction may play a role in cryptogenic strokes.

Abstract TP239: The Correlation Between Ultrasound Characteristics of Carotid Web and Ischemic Stroke

Objective: Carotid web is one of the etiologic factors contributed to cryptogenic ischemic stroke. This study aimed to analyze the correlation between ultrasound characteristics of carotid web and ischemic stroke (IS). Methods: Patients with carotid web initially examined by ultrasonography (US), confirmed by computed tomography angiography (CTA) subsequently, were retrospectively enrolled from January 2018 to July 2018. All patients were divided into IS group and no IS (NIS) group for comparative analysis. The degree of carotid artery stenosis (CAS) caused by the carotid web, and the angle between web and carotid wall were measured. The incidence of CAS &gt; 50%, web angle &lt; 70°, and the thrombus occurrence between the two groups were compared. Results: A total of 24 patients finally diagnosed with carotid web were enrolled (10 in IS group, 14 in NIS group). The mean age was 57 years (range 30-75 years), 14 patients were male (58.3%). Thirteen patients diagnosed with carotid web through initial US examination (54.2%, 13/24), and all other 11 patients (45.8%) were misdiagnosed as ulcer-plaque (9 patients) and dissection (2 patients) prior to final diagnosis. There was no significant difference in the incidence of CAS &gt; 50% between IS and NIS groups (10% versus 35.7%, P=0.341). The incidence of thrombus occurrence in IS group was higher than NIS group (80% versus 35.7%, P=0.047). In addition, the proportion of web angle ≤ 70° in IS group was higher than NIS group (90% versus 42.9%, P=0.033). Patients with web angle ≤ 70° had a higher incidence of thrombus than those angle &gt; 70° (73.3% versus 22.2%, P=0.033). However, the incidence of CAS &gt; 50% was higher in patients with web angle &gt; 70° (55.6% vs 6.7%, P=0.015). Conclusion: Ultrasonography could evaluate the specific imaging characteristics of carotid web. The web angle &gt; 70° accounted for CAS &gt; 50%. The angle ≤ 70° was related to developing thrombus, which may cause recurrent ischemic stroke.

Investigation of risk factors in cryptogenic ischemic stroke

Investigation of risk factors in cryptogenic ischemic stroke

Prothrombin G20210A polymorphism in patients with venous and cryptogenic arterial strokes among ethnic groups in south and north India.

Prothrombin (PT) G20210A is one of the genetic polymorphisms associated with thrombophilia. Studies show a low prevalence for this polymorphism in Asian populations with only one subject reported from India. We studied the prevalence and association of this polymorphism in patients with arterial and venous strokes and their matched controls in south and north India. We recruited patients with cerebral venous thrombosis (mean age 37.2 years) and cryptogenic ischaemic stroke (mean age 36.7 years), and age- and sex-matched controls (mean age 37.6 years) from south and north India. Genotyping was carried out using polymerase chain reaction followed by restriction fragment length polymorphism, and the prevalence of the variants among the patients and controls was compared. The heterozygous allele of the polymorphism was detected in both groups with significantly higher prevalence among north Indians (5/154; 3.2%) compared with south Indians (4/516; 0.8%; p = 0.026). Thrombosis as a manifestation of this polymorphism was more among north Indians with 4/82 (4.9%) of patients with ischaemic stroke and cerebral venous thrombosis having this polymorphism compared with south Indian patients 1/72 (1.4%), p = 0.003. PT G20210A is prevalent in India, especially among those from north India. Its role in predisposition to thrombosis needs to be studied further along with other known risk factors.

Transesophageal Echocardiography in Patients of Acute Ischemic Stroke

Background: Approximtely one third of cases of acute ischemic stroke are of undetermined etiology (cryptogenic). Among these cases, cardio embolic tend to be more severe than other causes. Transthoracic echocardiography is used as a standard imaging modality to study structural aspects of heart, however, transesophageal echocardiography (TEE) is a better and much more yielding modality. The present study was carried out in a tertiary care multispecialty hospital to enumerate the findings on TEE in the patients undergoing TEE for “cryptogenic stroke.” Methods: This retrospective observational study was done at our echo lab based on the TEE data of the last 10 years. Sixty-one consecutive adult patients admitted under department of neurology with a diagnosis of acute ischemic stroke and referred for TEE were included in the study. Results: Sixty one consecutive patients of cryptogenic acute ischemic stroke undergoing TEE were studied. Overall, 33% patients had grossly normal TEE findings. Patent foramen ovale (PFO) was the commonest abnormal finding present in 36%, atrial septal aneurysm (ASA) in 18% and both PFO and ASA were present in 18%. No statistical difference was noted between young (0-50 years) and elderly patients (&gt;50 years) with respect to inter atrial septum abnormalities. Twenty eight percent had atheroma in descending aorta. Left atrial appendage clot or spontaneous echo contrast was present in 5% and vegetation was present in 5%. Conclusion: Dilated left atrium was present in 16% and left ventricular dysfunction was present in 18% of the patients. Our results reinforce the idea of a TEE examination in all patients of ischemic stroke which are not explained by routine clinical evaluation and transthoracic echo.

Survey of Current Management Practices for Carotid Webs.

Background: Carotid webs are thick, fibrous intimal bands that appear as intraluminal shelf-like defects at the carotid bifurcation on vascular imaging. These lesions are a potential underrecognized cause of cryptogenic ischemic stroke. Although the recognition of carotid webs has increased, no evidence-based treatment guidelines are available. We surveyed subspecialists across multiple neurologic disciplines to assess the state of current clinical practice.Methods: An 8-question multiple-choice style survey of neurologists and radiologists assessed familiarity with this disease entity, preferred imaging modalities, and management strategies for asymptomatic and symptomatic (producing stroke) carotid webs. Responses were collected through SurveyMonkey software via anonymous responses to a posted survey link on the Society of Neurointerventional Surgery website in addition to invitation emails sent to colleagues in corresponding fields.Results: Of the 74 total respondents, 64% identified as neurointerventionalists. Respondents identified computed tomography angiography as the most commonly used imaging modality to place carotid webs in the differential diagnosis (57% of respondents’ preference), while conventional digital subtraction angiogram was the preferred modality to confirm a web (54% of respondents’ preference). Respondents preferred single and dual antiplatelet therapy to manage asymptomatic and acute stroke-producing carotid webs, while invasive treatment was most commonly sought for webs producing recurrent strokes.Conclusion: Familiarity with carotid webs varied across subspecialties. We found some consensus among respondents on the imaging modality preferred to identify webs, on asymptomatic carotid web management, and on recurrently symptomatic (multiple strokes) carotid web management. Less consistency was seen regarding preferences for confirmatory imaging and management of acutely symptomatic (initial stroke) carotid webs.

Transcranial Doppler to detect right-to-left shunt in cryptogenic acute ischemic stroke.

ObjectivesWe aimed to confirm the sensitivity and specificity of contrast transcranial Doppler (cTCD) in the detection of right‐to‐left shunt (RLS) compared to the current reference standard (i.e., transesophageal echocardiography—TEE) in patients aged <55 years with a cryptogenic acute ischemic stroke (AIS) or high‐risk (ABCD 2 score ≥4) transient ischemic attack (TIA), and to calculate the real life delay in detecting RLS by cTCD versus TEE in a tertiary care academic stroke center.MethodsConsecutive 16‐ to 54‐year‐old patients with AIS or high‐risk TIA underwent complete diagnostic workup which included, in case of undetermined etiology, cTCD and TEE. Sensitivity and specificity of cTCD, RLS characteristics, and median delay between the two tests were calculated.ResultsOf the 98 included patients, 52 (53%) had a cryptogenic cerebrovascular ischemic event, which displayed a 56% prevalence of RLS related to a patent foramen ovale (PFO) mainly with a high‐grade shunt. When comparing TCD with “bubble test” to TEE, sensitivity and specificity were both 100%. Median delays from symptom onset to examination were 2 (min–max 1–10) and 21 (min–max 1–60) days, respectively, for cTCD and TEE. No adverse event occurred during or after cTDC examination.ConclusionsTranscranial Doppler with “bubble test” appears as the best screening test for the detection of RLS in young and middle‐aged adults with cryptogenic acute cerebral ischemic events to select patients potentially suitable for closure procedure after TEE confirmation.

Pathogenic variants in the ABCC6 gene are associated with an increased risk for ischemic stroke.

Ischemic stroke causes a high mortality and morbidity worldwide. It results from a complex interplay of incompletely known environmental and genetic risk factors. We investigated the ABCC6 gene as a candidate risk factor for ischemic stroke because of the increased ischemic stroke incidence in the autosomal recessive disorder pseudoxanthoma elasticum, caused by biallelic pathogenic ABCC6 variants, the higher cardiovascular risk in heterozygous carriers and the established role of ABCC6 dysfunction in myocardial ischemia. We established segregation of a known pathogenic ABCC6 variant (p.[Arg1314Gln]) in 11/19 family members of an ischemic stroke patient in a large multigenerational family suffering from ischemic stroke and/or cardiovascular disease at a relatively young age. In an independent case-control study in 424 ischemic stroke patients and 250 healthy controls, pathogenic ABCC6 variants were 4.9 times more frequent (P = 0.036; 95% CI 1.11-21.33) in the ischemic stroke patient cohort. To study cellular consequences of ABCC6 deficiency in the brain, immunostaining of brain sections in Abcc6-deficient mice and wild-type controls were performed. An upregulation of Bmp4 and Eng and a downregulation of Alk2 was identified in Abcc6-/- mice, suggesting an increase in apoptosis and angiogenesis. As both of these processes are induced in ischemia, we propose that a pro-ischemic state may explain the higher risk to suffer from ischemic stroke in patients carrying a pathogenic ABCC6 variant, as this may lower the threshold to develop acute ischemic events in these patients. In conclusion, this study identified heterozygous ABCC6 variants as a risk factor for ischemic stroke. Further, dysregulation of Bmp (Bmp4, Alk2) and Tgfβ (Eng) signaling in the brain of Abcc6-/- mice could lead to a pro-ischemic state, lowering the threshold to develop acute ischemic events. These data demonstrate the importance of a molecular analysis of the ABCC6 gene in patients diagnosed with cryptogenic ischemic stroke.

Complex Left Atrial Appendage Morphology Is an Independent Risk Factor for Cryptogenic Ischemic Stroke.

Importance: Ischemic strokes pose a significant health burden. However, the etiology of between 20 and 40% of these events remains unknown. Left atrial appendage morphology may influence the occurrence of thromboembolic events.Design: A retrospective cross-sectional study was conducted to investigate the role of LAA morphology in patients with atrial fibrillation (AF) and cardioembolic-associated stroke and patients with cryptogenic stroke without atrial fibrillation. LAA morphology is classified into two groups: (1) simple (chicken-wing) vs. (2) complex (non-chicken wing) based on transesophageal echocardiography (TEE) findings. In addition to the LAA morphology, left atrial parameters, including orifice diameter, depth, emptying velocity, and filling velocity, were collected for both groups. Mathematical, computational models were constructed to investigate flow velocities in chicken-wing and non-chicken wing morphological patterns to assess LAA function further.Findings: TEE values for volume, size, emptying, and filling velocities were similar between simple and complex LAA morphology groups. Patients with cryptogenic stroke without coexisting AF were noted to have significantly higher rates of complex LAA morphology. Chicken-wing LAA morphology was associated with four-fold higher flow rate (kg/s) in computational simulations.Conclusions: Complex LAA morphology may be an independent contributing factor for cryptogenic strokes. Further studies are warranted to investigate the mechanism involved in LAA morphology and thromboembolic events.