Field, Thalia S.

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.

With improvement in medical and surgical care, the number of adults with congenital heart disease (CHD) is soaring. Adults with CHD commonly have impairments in brain health. However, significant gaps in knowledge remain regarding the relevant types and prevalence of neurologic and psychiatric risk and their associated risk factors. We sought to review current evidence, identify gaps in knowledge, and develop key next steps to improve scientific understanding and clinical care. Three working groups—Genetics and Brain Health, Characterizing Neuropsychological and Psychological Outcomes, and Neuropsychological and Psychosocial Interventions—were composed of multidisciplinary experts in relevant clinical and research domains, as well as adults with CHD. Each group identified 5 key knowledge gaps and associated next investigations needed to address those gaps. For Genetics and Brain Health, 5 key knowledge gaps were identified: lack of a standardized neuroimaging protocol for adults with CHD, need to understand neuroradiological–pathological–neuropsychological correlates, role of gene–environment interactions, what can be learned from brain health risk models from other groups, and how existing multimodal approaches influence risk and neuroresilience. Adults with CHD can benefit from routine assessment of brain health, as well as increased clinical and basic research into the underlying factors that contribute to risk and neuroresilience for neurologic and psychiatric sequalae. Multidisciplinary collaborative efforts that incorporate adults with CHD across the research cycle are essential for all key next steps.

BACKGROUND: Small, randomized trials of patients with cervical artery dissection showed conflicting results regarding optimal stroke prevention strategies. We aimed to compare outcomes in patients with cervical artery dissection treated with antiplatelets versus anticoagulation. METHODS: This is a multicenter observational retrospective international study (16 countries, 63 sites) that included patients with cervical artery dissection without major trauma. The exposure was antithrombotic treatment type (anticoagulation versus antiplatelets), and outcomes were subsequent ischemic stroke and major hemorrhage (intracranial or extracranial hemorrhage). We used adjusted Cox regression with inverse probability of treatment weighting to determine associations between anticoagulation and study outcomes within 30 and 180 days. The main analysis used an as-treated crossover approach and only included outcomes occurring with the above treatments. RESULTS: The study included 3636 patients (402 [11.1%] received exclusively anticoagulation and 2453 [67.5%] received exclusively antiplatelets). By day 180, there were 162 new ischemic strokes (4.4%) and 28 major hemorrhages (0.8%); 87.0% of ischemic strokes occurred by day 30. In adjusted Cox regression with inverse probability of treatment weighting, compared with antiplatelet therapy, anticoagulation was associated with a nonsignificantly lower risk of subsequent ischemic stroke by day 30 (adjusted hazard ratio [HR], 0.71 [95% CI, 0.45–1.12]; P =0.145) and by day 180 (adjusted HR, 0.80 [95% CI, 0.28–2.24]; P =0.670). Anticoagulation therapy was not associated with a higher risk of major hemorrhage by day 30 (adjusted HR, 1.39 [95% CI, 0.35–5.45]; P =0.637) but was by day 180 (adjusted HR, 5.56 [95% CI, 1.53–20.13]; P =0.009). In interaction analyses, patients with occlusive dissection had significantly lower ischemic stroke risk with anticoagulation (adjusted HR, 0.40 [95% CI, 0.18–0.88]; P interaction =0.009). CONCLUSIONS: Our study does not rule out the benefit of anticoagulation in reducing ischemic stroke risk, particularly in patients with occlusive dissection. If anticoagulation is chosen, it seems reasonable to switch to antiplatelet therapy before 180 days to lower the risk of major bleeding. Large prospective studies are needed to validate our findings.

BACKGROUND: It is uncertain whether antiplatelets or anticoagulants are more effective in preventing early recurrent stroke in patients with cervical artery dissection. Following the publication of the observational Antithrombotic for STOP-CAD (Stroke Prevention in Cervical Artery Dissection) study, which has more than doubled available data, we performed an updated systematic review and meta-analysis comparing antiplatelets versus anticoagulation in cervical artery dissection. METHODS: The systematic review was registered in PROSPERO (CRD42023468063). We searched 5 databases using a combination of keywords that encompass different antiplatelets and anticoagulants, as well as cervical artery dissection. We included relevant randomized trials and included observational studies of dissection unrelated to major trauma. Where studies were sufficiently similar, we performed meta-analyses for efficacy (ischemic stroke) and safety (major hemorrhage, symptomatic intracranial hemorrhage, and death) outcomes using relative risks. RESULTS: We identified 11 studies (2 randomized trials and 9 observational studies) that met the inclusion criteria. These included 5039 patients (30% [1512] treated with anticoagulation and 70% [3527]) treated with antiplatelets]. In meta-analysis, anticoagulation was associated with a lower ischemic stroke risk (relative risk, 0.63 [95% CI, 0.43 to 0.94]; P =0.02; I 2 =0%) but higher major bleeding risk (relative risk, 2.25 [95% CI, 1.07 to 4.72]; P =0.03, I 2 =0%). The risks of death and symptomatic intracranial hemorrhage were similar between the 2 treatments. Effect sizes were larger in randomized trials. There are insufficient data on the efficacy and safety of dual antiplatelet therapy or direct oral anticoagulants. CONCLUSIONS: In this study of patients with cervical artery dissection, anticoagulation was superior to antiplatelet therapy in reducing ischemic stroke but carried a higher major bleeding risk. This argues for an individualized therapeutic approach incorporating the net clinical benefit of ischemic stroke reduction and bleeding risks. Large randomized clinical trials are required to clarify optimal antithrombotic strategies for management of cervical artery dissection.

BACKGROUND: Patients presenting with cervical artery dissection (CAD) are at risk for subsequent ischemic events. We aimed to identify characteristics that are associated with increased risk of ischemic stroke after initial presentation of CAD and to evaluate the differential impact of anticoagulant versus antiplatelet therapy in these high-risk individuals. METHODS: This was a preplanned secondary analysis of the STOP-CAD study (Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection), a multicenter international retrospective observational study (63 sites from 16 countries in North America, South America, Europe, Asia, and Africa) that included patients with CAD predominantly between January 2015 and June 2022. The primary outcome was subsequent ischemic stroke by day 180 after diagnosis. Clinical and imaging variables were compared between those with versus without subsequent ischemic stroke. Significant factors associated with subsequent stroke risk were identified using stepwise Cox regression. Associations between subsequent ischemic stroke risk and antithrombotic therapy type (anticoagulation versus antiplatelets) among patients with identified risk factors were explored using adjusted Cox regression. RESULTS: In all, 4023 patients (mean age was 47.4 years; 44.5% were women) were included. By day 180, subsequent ischemic stroke occurred in 5.3% of the cohort. In adjusted Cox regression, factors associated with increased risk of subsequent ischemic stroke were prior history of ischemic stroke (adjusted hazard ratio [aHR], 7.31 [95% CI, 1.61–33.13]; P =0.010), presentation within 7 days from first symptoms (aHR, 3.04 [95% CI, 1.04–8.91]; P =0.043), infarct on baseline imaging (aHR, 9.85 [95% CI, 3.65–26.58]; P <0.001), and occlusive dissection (aHR, 2.34 [95% CI, 1.03–5.34]; P =0.043). Only patients with occlusive dissection demonstrated a reduced risk of subsequent ischemic stroke when treated with anticoagulation versus antiplatelets (aHR, 0.36 [95% CI, 0.16–0.80]; P =0.01). CONCLUSIONS: In this post hoc analysis of the STOP-CAD study, several factors associated with subsequent ischemic stroke were identified among patients with CAD. Furthermore, we identified a potential benefit of anticoagulation in patients with CAD with occlusive dissection. These findings require validation by meta-analyses of prior studies to formulate optimal treatment strategies for specific high-risk CAD subgroups.

Background Although intravenous thrombolysis (IVT) is safe and effective in populations with general stroke, its impact on cervical artery dissection–related acute ischemic stroke (CeAD‐AIS) remains unclear. This retrospective study used the National Inpatient Sample to compare outcomes in patients with CeAD‐AIS treated with and without IVT. Methods We included adult patients with concurrent CeAD and AIS diagnoses ( International Classification of Diseases, Tenth Revision [ ICD‐10 ], codes) hospitalized from 2016 to 2019. The primary outcome was home discharge; safety outcomes included inpatient death and intracerebral hemorrhage. We performed survey‐weighted multivariable logistic regressions comparing IVT versus no IVT, followed by interaction analyses to examine effect modifications based on age, medical history, stroke severity, carotid artery involvement, and endovascular treatment. Results Between 2016 and 2019, 1360 (12.1%) of 11 285 patients with CeAD‐AIS received IVT. IVT‐treated patients had higher median National Institutes of Health Stroke Scale scores (median [interquartile range], 8 [4–17] versus 3 [1–11]; P <0.001). Adjusted analyses showed IVT was associated with higher odds of home discharge (adjusted odds ratio [OR], 1.40 [95% CI, 1.01–1.92]; P =0.042), but not with inpatient death (adjusted OR, 1.29 [95% CI, 0.76–2.20]; P =0.347) or intracerebral hemorrhage (adjusted OR, 0.69 [95% CI, 0.32–1.48]; P =0.341). Stroke severity ( P for interaction=0.001) and carotid artery involvement ( P for interaction=0.021) significantly modified IVT's effect on home discharge, with IVT being associated with an increased likelihood of home discharge in patients with moderate to severe strokes (National Institutes of Health Stroke Scale score >4) and carotid artery involvement. Conclusions IVT improves the likelihood of home discharge in patients with CeAD‐AIS without increasing the risk of inpatient death or intracerebral hemorrhage.

Introduction: The safety and efficacy of intravenous thrombolysis (IVT) in cervical artery dissection-related acute ischemic stroke (CeAD-AIS) remains unclear. We performed a retrospective study of data from the National Inpatient Sample investigating outcomes in CeAD-AIS patients treated with and without IVT. Methods: We included adult patients with CeAD-AIS hospitalized between 2016 to 2019. CeAD-AIS was defined by concurrent CeAD and AIS diagnoses, identified with ICD-10 codes. The primary outcome was home discharge. The safety outcomes were inpatient death and intracerebral hemorrhage (ICH). We used survey-weighted multivariable adjusted logistic regressions comparing the groups (IVT versus no IVT), followed by interaction analyses to examine for effect modifications based on age, medical history, stroke severity, and endovascular treatment. Results: Between 2016-2019, 1,360 (12.1%) of 11,285 CeAD-AIS patients received IVT. Patients treated with IVT- had higher NIH Stroke Scale (NIHSS) scores (median 8 [4-17] versus 3 [1-11]; p < 0.001). In adjusted analyses, treatment with IVT was associated with a greater odds of home discharge (adjusted odds ratio [aOR] 1.49; 95% confidence interval [CI] 1.09-2.05, p = 0.014), but not ICH (aOR 0.90, 95% CI 0.43-1.86, p = 0.773) or inpatient death (aOR 1.22, 95% CI 0.72-2.06, p = 0.454). In interaction analyses, stroke severity significantly interacted with IVT ( p for interaction = 0.001), where IVT was significantly associated with increased likelihood of home discharge in patients with moderate to severe strokes (NIHSS > 4) (aOR 2.28, 95% CI 1.59-3.26, p < 0.001) but not in those with mild stroke (NIHSS 0-4) (aOR 1.03 95% CI 0.62-1.70, p = 0.922). Conclusion: IVT improved the likelihood of home discharge in patients with CeAD-AIS without increasing the risk of inpatient death or ICH.

Growing evidence suggests a consistent association between atrial fibrillation (AF) and cognitive impairment and dementia that is independent of clinical stroke. This report from the AF-SCREEN International Collaboration summarizes the evidence linking AF to cognitive impairment and dementia. It provides guidance on the investigation and management of dementia in patients with AF on the basis of best available evidence. The document also addresses suspected pathophysiologic mechanisms and identifies knowledge gaps for future research. Whereas AF and dementia share numerous risk factors, the association appears to be independent of these variables. Nevertheless, the evidence remains inconclusive regarding a direct causal effect. Several pathophysiologic mechanisms have been proposed, some of which are potentially amenable to early intervention, including cerebral microinfarction, AF-related cerebral hypoperfusion, inflammation, microhemorrhage, brain atrophy, and systemic atherosclerotic vascular disease. The mitigating role of oral anticoagulation in specific subgroups (eg, low stroke risk, short duration or silent AF, after successful AF ablation, or atrial cardiopathy) and the effect of rhythm versus rate control strategies remain unknown. Likewise, screening for AF (in cognitively normal or cognitively impaired patients) and screening for cognitive impairment in patients with AF are debated. The pathophysiology of dementia and therapeutic strategies to reduce cognitive impairment warrant further investigation in individuals with AF. Cognition should be evaluated in future AF studies and integrated with patient-specific outcome priorities and patient preferences. Further large-scale prospective studies and randomized trials are needed to establish whether AF is a risk factor for cognitive impairment, to investigate strategies to prevent dementia, and to determine whether screening for unknown AF followed by targeted therapy might prevent or reduce cognitive impairment and dementia.