Keser, Zafer

Abstract Background and aims Patient foramen ovale (PFO) is a stroke risk factor evaluated using transthoracic echocardiogram (TTE), transesophageal echocardiogram (TEE), transcranial Doppler ultrasound (TCD), and cardiac computed tomography (CCT). TCD is non-invasive, but its diagnostic performance relative to other modalities is unclear. We hypothesized that TCD has high sensitivity but low specificity for PFO detection. Methods We conducted an IRB-approved, single-center retrospective study of patients undergoing TCD for right-to-left shunt (RLS) detection between January 2024 and April 2025. Patients were identified from the Neurosonology Laboratory Quality Database. Records were reviewed for demographics, comorbidities, and TTE, TEE, and CCT findings. Sensitivity, specificity, and positive and negative predictive values were calculated for TCD, TTE, and CCT relative to TEE, the gold standard. The sensitivity and specificity of TCD versus TTE were compared using McNemar test. Results Ninety-two patients were included. Mean age was 52.66 ± 15.78 years, and 51% were female; qualifying events included ischemic stroke or transient ischemic attack. RLS was detected in 53 patients (57.6%) by TCD, 17 (30%) by TTE, 18 (28.5%) by TEE, and 3 (21%) by CCT. TCD demonstrated 94% sensitivity and 53% specificity, (PPV 66%, NPV 89%). TTE showed 50% sensitivity and 82% specificity (PPV: 75%, NPV 61%), while CCT showed 33% sensitivity and 100% specificity (PPV 100%, NPV 33.3%). TCD had significantly higher sensitivity than TTE for RLS detection (p=0.039) with a non-significant difference in specificity (p=0.062), using TEE as the reference. Conclusions TCD has high sensitivity for RLS detection in patients with ischemic stroke or transient ischemic attack. Conflict of interest Rachel Knopp: nothing to disclose; Kelly Flemming: nothing to disclose; Eugene Scharf: nothing to disclose; Zafer Keser: nothing to disclose; Jessica Prink: nothing to disclose; Shari Johnson: nothing to disclose; Guy Reeder: nothing to disclose; Robert Brown: nothing to disclose; William Harmsen: nothing to disclose; Muhib Khan: nothing to disclose Table 1 - belongs to Results

Background: Stroke is a leading cause of mortality and long-term disability, and aphasia is among its most common and debilitating sequelae. Diffusion tensor imaging (DTI) and advanced diffusion imaging techniques enable the assessment of white matter integrity and provide clinically relevant measures in post-stroke aphasia. Methods: We conducted a comprehensive review of studies applying DTI or advanced diffusion imaging to investigate structural connectivity in adults with post-stroke aphasia (PSA). PubMed, CENTRAL, Ovid MEDLINE, and Embase were searched, and eligible studies were synthesized according to their diagnostic, prognostic, or therapeutic focus. Results: Ninety-five studies were included. Of these, 59 were classified as diagnostic, 17 as prognostic, and 19 as therapeutic. Most studies employed conventional DTI (n = 77), while a growing body of research utilized advanced diffusion models, including CSD, DSI, and DKI (n = 18). Conclusions: This comprehensive synthesis demonstrates the evolution of diffusion imaging in PSA research. While conventional DTI has provided foundational insights, advanced diffusion methods offer superior characterization of complex fiber architecture and improved clinical–anatomical correlation. Diffusion-derived markers of dorsal and ventral language pathways were consistently associated with language performance, while connectome-level analyses highlighted the importance of preserved global network architecture for recovery. Continued efforts are needed to translate diffusion imaging findings into clinical applicable biomarkers to guide personalized aphasia rehabilitation, with greater use of advanced methods.

Introduction Cerebellar transcranial direct current stimulation (tDCS) combined with language therapy can aid in chronic aphasia recovery, but the neural mechanisms and biomarkers of treatment efficacy remain uncertain. Methods In this secondary analysis of data from a previously conducted clinical trial, we used a randomized, double-blind, sham-controlled, within-subject crossover design with a study sample of 19 participants with post-stroke aphasia. We assessed the degree to which baseline properties of cerebro-cerebellar white matter tracts can predict or moderate longitudinal treatment effects at three time points: post-treatment, 2 weeks post-treatment, and 2 months post-treatment. Tract properties were measured by fractional anisotropy (FA) and mean diffusivity (MD) from diffusion tensor imaging (DTI). We also tested whether there are differential effects between trained and untrained language tasks and between cerebellar tDCS polarity (anodal and cathodal). Results Baseline measures of tracts connecting the left lesioned cortex to the right posterolateral cerebellum (stimulation target) influenced treatment gains for untrained tasks, relative to sham control. In contrast, for the trained task, treatment gains were influenced by baseline measures of tracts connecting the non-stimulated left cerebellum with the contralateral right cerebral cortex. Although there were no consistent effects from cerebellar tDCS polarity, a highly consistent pattern emerged across all tasks and tracts. Specifically, language improvements were predicted by a baseline tract profile (i.e., higher FA and lower MD) typically associated with higher white matter integrity, especially within the context of stroke-induced white matter decline. Discussion These findings corroborate the potential for baseline tract properties as a biomarker of treatment efficacy and support the notion that adjuvant (cerebellar tDCS + language) therapy preferentially benefits individuals with relatively preserved structural connections within functionally relevant networks. Clinical trial registration ClinicalTrials.gov , identifier (NCT02901574).

Background and Objectives: Cervical artery dissection (CeAD) is a leading cause of ischemic stroke in younger adults, yet sex-specific variations in its clinical presentation, imaging characteristics, and outcomes remain underexplored. We aimed to evaluate these differences using data from a large, multicenter registry. Methods: We analyzed data from the STOP-CAD registry, which includes patients with radiologically confirmed non-traumatic CeAD enrolled between 2015 and 2021 across multiple centers. Clinical and imaging characteristics were compared between men and women using multivariable logistic regression. Outcomes assessed included ischemic stroke recurrence at 180 days, excellent functional outcome (modified Rankin Scale [mRS] 0–1) at 90 days, symptomatic intracerebral hemorrhage (sICH), and mortality. Results: Among 4,023 patients with CeAD, 1,783 (44.6%) were women. Compared to men, women were younger (median age: 42 vs 50 years), more likely to have a history of migraine (26.9% vs 8.3%) and connective tissue disorders (14.3% vs 5.8%), and presented more frequently with non-ischemic symptoms such as headache, neck pain, or tinnitus (adjusted OR [aOR] 2.0; 95% CI, 1.8–2.3; p<0.001). Women had significantly higher odds of vertebral artery dissection (OR, 1.3; 95% CI, 1.2-1.5; p<0.001), multivessel involvement (OR, 2.1; 95% CI, 1.7-2.5; p<0.001), and pseudoaneurysm formation (OR, 1.3; 95% CI, 1.1-1.6; p=0.003). Despite these differences, there was no significant sex-based difference in key clinical outcomes: excellent functional recovery at 90 days (OR 0.94; 95% CI 0.76-1.15 p=0.542), ischemic stroke recurrence at 180 days (OR 0.56 CI 0.23-1.3 p=0.213), or mortality (OR 0.83; 95% CI 0.47-1.48, p=0.529). Conclusion: In this large international cohort, we observed women with CeAD were younger, more likely to present with non-ischemic symptoms with distinct imaging features. These underscore the need for heightened clinical suspicion of CeAD in women presenting with atypical symptoms, even in the absence of ischemic deficits or conventional vascular risk factors, and suggest that sex-specific phenotyping may enhance diagnostic accuracy and early management.

Background: Patients with cervical artery dissection (CAD) have a higher prevalence of cerebral aneurysms, likely due to underlying vasculopathies. Understanding risk factors and outcomes in this population may inform screening and management strategies. Methods: We conducted a post-hoc analysis of the STOP-CAD study, a multicenter international registry of patients with non-major trauma-related CAD across 63 centers. Cerebral aneurysms were identified based on medical history and intracranial vascular imaging obtained for dissection diagnosis. We compared demographic, clinical, laboratory, and imaging characteristics between patients with and without aneurysms. Variables with p<0.05 in univariate analysis were entered into a multivariable binary logistic regression to identify independent predictors. Clinical outcomes including ischemic stroke and symptomatic intracranial hemorrhage at follow-up were compared between both groups. Results: Out of 4023 patients included in the STOP-CAD study, 116 (2.9%) had at least one incidental cerebral aneurysm. In adjusted binary logistic regression, patients with cerebral aneurysm were more likely to have a history of migraine (aOR 1.78 95% CI 1.15-2.75, p=0.009), history of hypertension (aOR 1.65 95% CI 1.12-2.43, p = 0.010), known connective tissue disorder (aOR 3.47 95% CI 1.71-7.03), history of dissection (aOR 2.63 95% CI 1.31-5.28, p = 0.007), and a dissecting aneurysm at the site of the dissection (aOR 1.94 95% CI 1.25-3.01, p = 0.003). At follow-up, the presence of a cerebral aneurysm was not associated with ischemic stroke (7.8% vs. 5.6% p>0.1), but with a trend towards increased odds of symptomatic intracranial hemorrhage (3.4% vs. 1.2%, p = 0.062). Conclusions: Patients with CAD and concurrent incidental cerebral aneurysm were more likely to have a history of migraine headaches and markers of underlying vasculopathy and had a non-significantly increased risk of intracranial hemorrhage at follow-up. Further studies are needed to identify best practices for surveillance and risk stratification in this subgroup.

Background: Cervical artery dissection (CeAD) accounts for nearly 25% of all ischemic strokes in young adults. CeAD can lead to the development of dissecting aneurysms (DA). However, the incidence, risk factors and outcomes of CeAD patients with DA is not well established. This study aims to identify risk factors for developing DA, subsequent growth, and impact on patient outcomes. Methods: This is a secondary analysis of the Antithrombotics for Stroke Prevention in Cervical Artery Dissection (STOP-CAD), a multicenter cross-sectional international retrospective study. CeAD patients were stratified for the presence of DA. We used multivariable regression to identify factors associated with DA. Patients with DA were further analyzed for DA growth. The primary outcome was ischemic stroke after CeAD+DA diagnosis. Secondary outcomes included ischemic stroke after CeAD+DA with DA growth. Multivariable logistic regression analysis was used to assess the association between DA and risk factors. We also performed univariate Cox regression and generated Kaplan-Meier survival curves comparing study outcomes based on presence of DA and subsequent growth. Results: Of the 4023 patients included in the STOP-CAD study, 4008 were included in this analysis and 767 (19%) patients had DA (546 with DA on initial presentation). Patients with DA had a mean age of 46 [IQR 37-55] years and 50% (383) were women. In combined adjusted analyses, DA patients were more often non-Hispanic (aOR 0.63, 95% CI 0.41-0.94, p<0.02), more commonly had a history of migraine (aOR 1.27, 95% CI 1.01-1.59, p=0.037), connective tissue disorder (aOR 2.02, 95% CI 1.22-3.36, p=0.007), minor neck trauma (aOR 1.70, 95% CI 1.29-2.26, p<0.001) and were more likely to present with ischemic stroke (aOR 1.73, 95% CI 1.05-2.87, p=0.031). DA growth was noted in 55 out of 546 (10%) patients with DA on presentation. There was no significant difference in the risk of ischemic stroke by day 180 in patients with DA (hazard ratio [HR] 0.92 [95% CI, 0.65-1.30]; P =0.63) or DA growth (HR 2.40, [95% CI, 0.79-7.24]; P =0.12). Conclusion: In this subanalysis of STOP-CAD, nearly one in five patients with CeAD developed a DA. Factors associated with a higher likelihood of DA included non-Hispanic ethnicity, history of migraine, connective tissue disorder, minor neck trauma, and ischemic stroke at presentation. DA diagnosis and DA growth did not impact the risk of subsequent ischemic stroke at 6 months.

Background: The clinical characteristics and complications associated with de novo pseudoaneurysm formation beyond the acute phase of cervical artery dissection remain poorly defined. In this study, we examined the incidence, risk factors, and related ischemic and hemorrhagic events of post-acute de novo pseudoaneurysm formation. Methods: We analyzed data from the STOP-CAD study (Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection). A de novo pseudoaneurysm was defined as a new (not present on initial imaging) focal enlargement in the diameter of the artery, greater than the native lumen. The incidence of de novo pseudoaneurysm was assessed at 90 days, 180 days, and beyond 180 days of follow-up. Univariate and multivariate regression analyses were conducted to identify risk factors for post-acute de novo pseudoaneurysm formation. Kaplan-Meier survival estimates were used to compare ischemic and hemorrhagic events between patients with and without de novo pseudoaneurysms. Results: Among 4008 patients, 546 were excluded as they had dissecting pseudoaneursyms on initial presentation. Therefore, 3,462 patients were included in this analysis of whom 220 patients (6.35%) developed a de novo pseudoaneurysm over a maximum follow-up of 4.4 years. Of these, 127 (57.72%) were detected within the first 90 days, and 172 (78.18%) within the first 180 days. In multivariate regression analyses, in addition to hypertension, active smoking and Hispanic ethnicity, fibromuscular dysplasia (FMD) was an independent risk factor for post-acute de novo pseudoaneurysm formation (adjusted OR: 2.160; 95% CI: 1.408–3.315; p < 0.001). Notably, the presence of a de novo pseudoaneurysm was not associated with a significant increase in ischemic (hazard ratio [HR] 1.43 [95% CI, 0.89–2.30]; P=0.14) or hemorrhagic events (hazard ratio [HR] 1.42 [95% CI, 0.43–4.69]; P=0.57). Conclusion: De novo pseudoaneurysm formation following a diagnosis of a cervical artery dissection is not uncommon and most frequently occurs within the first 180 days. FMD was independently associated with this complication. The development of a de novo pseudoaneurysm did not significantly increase the risk of subsequent ischemic or hemorrhagic events.

Background and Objectives: Pregnancy and the postpartum period increase the risk of cervical artery dissection (CEAD), a notable cause of stroke in young women. We aimed to describe the clinical presentation, imaging findings, and outcomes of CEAD occurring during pregnancy or shortly after delivery. Methods: We analyzed data from the STOP-CAD registry, a large international multicenter study of patients treated with antithrombotic therapy for non-traumatic CEAD between 2015 and 2021. This sub-study focused on women who were pregnant or within 12 weeks postpartum at the time of symptom onset. We assessed baseline clinical features, imaging results, acute stroke treatments, and functional outcomes. Results: Among 1,783 women in the registry, 62 (3.5%) had pregnancy-associated CEAD, with a median age of 34 years (IQR, 30-38). One-third had a history of migraine (33.9%), one-fifth had hypertension (21.0%), while other vascular risk factors were rare. Recent minor neck trauma was reported in 17.7%. Ischemic stroke symptoms occurred in 25 (40.3%) patients, and 23 (37.1%) had acute infarcts on imaging. However, most (59.7%) presented with non-ischemic symptoms. Vertebral artery dissections were more common than carotid dissections (62.9% vs. 48.4%), and 33.9% had multivessel involvement. Among patients presenting with ischemic stroke symptoms, 4 received thrombolysis and 7 underwent thrombectomy. Remarkably, 92% had excellent functional recovery (modified Rankin Score 0–1) at 90 days, and there were no stroke recurrences at 180 days. Conclusion: Pregnancy- and postpartum-associated CEAD is uncommon and associated with ischemic stroke in nearly half of patients. A history of migraine and hypertension may be potential risk factors. Despite the severity of presentation, most patients had favorable outcomes with timely treatment.

Background and Objectives: Cervical artery dissection (CeAD) is a common cause of ischemic stroke in young adults. We aim to identify age-based differences in clinical presentation, imaging findings, and outcomes after CeAD. Methods: This was a sub-study using the STOP-CAD registry, a multicenter cross-sectional international retrospective study of patients diagnosed with CeAD and treated with an antithrombotic from January 1, 2015 to December 31, 2021. Baseline clinical and imaging characteristics were compared between younger and older adults with CeAD (≤45 versus >45 years of age) using multivariable logistic regression. We chose this age cut off due to its frequent usage in stroke in the young literature. Multiple logistic regression models were used to determine association between young age and outcomes after CeAD (ischemic stroke at 180 days, excellent functional outcome with modified Rankin Scale of 0-1 at 90 days, and mortality) after adjusting for sex, vascular risk factors, CeAD characteristics, and NIHSS on presentation. Results: Among 4023 CeAD patients included in the study, 1901 (47.3%) were ≤45 years of age. Patients were followed for a median of 307 days (IQR 102-831). Young adults with CeAD were more likely to be women (Odds Ratio [OR], 2.4; 95% CI, 2.1-2.9; p<0.001), of Hispanic ethnicity (OR, 1.8; 95% CI 1.3-2.5; p<0.001), have a history of migraines (OR, 1.6; 95% CI, 1.3-2.0; p<0.001) and recent neck trauma (OR, 1.6; 95% CI, 1.3-1.9; p<0.001) while having fewer traditional vascular risk factors. Young adults with CeAD had higher odds of a non-ischemic presentation (OR, 1.3; 95% CI, 1.1-1.5; p=0.013), vertebral artery dissection (OR 2.5; 95% CI, 2.2-3.0; p<0.001), and multivessel involvement (OR 1.5; 95% CI, 1.1-1.9; p=0.004). In adjusted analysis, younger age was not associated with an increased risk of recurrent ischemic stroke (adjusted Hazard Ratio [HR], 0.48; 95% CI 0.2-1.2; p=0.119). Younger age was associated with significantly greater odds of excellent functional outcome at 90 days (aOR, 1.48; 1.20-1.84, p<0.001) and lower risk of death at follow up (aHR, 0.37; 95% CI, 0.17-0.81; p=0.012) after CeAD. Conclusion: In a large international cohort, young adults with CeAD had a distinct clinical phenotype with higher odds of non-ischemic presentation, vertebral artery dissection, and multivessel involvement while having fewer traditional vascular risk factors. Young adults had a decreased odds of disability and mortality after CeAD.