The HSACat Project: A Prospective Multicenter Observational Study of Spontaneous Subarachnoid Hemorrhage in Catalonia, Spain.

BACKGROUND: Incidence, clinical course, and fatality of spontaneous subarachnoid hemorrhage (SAH) are evolving, with prevalence of risk factors diminishing, implementation of early detection programs and strategies for priority aneurysm exclusion, technical refinement with less invasive procedures, and improvements in neurocritical care. Modern epidemiological and prognostic data are lacking, especially in southern European and Mediterranean populations. METHODS: A prospective multicenter observational study on SAH was held in Catalonia, Northeast Spain, from 2020 to 2022 (HSACat project). All public tertiary hospitals participated in a common registry. Primary end points were functional outcomes (modified Rankin Scale) and mortality at 12 months. Secondary aims included epidemiological data, passage of patients between referral and tertiary hospitals, diagnostic and treatment delays, and in-hospital complications. RESULTS: Of 550 SAH cases reported in Catalonia (2020-2022), a complete registry for analysis was available for 474. Death rate was 20.6% during hospital admission and 26.9% at 1 year. Good functional outcome (modified Rankin Scale score 0-2) was observed in 63.4%, 70.1%, and 76.0% at 3, 6, and 12 months. Age at presentation was younger in men, patients who smoked, and patients with hypertension (P < 0.05). The female-to-male ratio was 3:2 except in the nonaneurysmal group. Time from onset to tertiary hospital admission was longer in rural than in metropolitan areas (7.0 hours vs. 4.7 hours, P < 0.01). Aneurysm occlusion in the first 72 hours was achieved in 83.3%; mainly endovascularly (77.5%) followed by microsurgically (19.3%). CONCLUSIONS: Even when most patients received timely aneurysm treatment, case fatality rates were considerably high. Data provided by the HSACat project may have public health effects and be used to guide prevention programs and screening strategies.

Prevalence and Factors Associated with Carotid Stenosis in Acute Ischemic Stroke Patients with Atrial Fibrillation.

INTRODUCTION: Among stroke patients with atrial fibrillation (AF), it is not uncommon to identify carotid atherosclerosis. This study aimed to estimate the prevalence of, and factors associated with, carotid atherosclerosis among patients with AF and acute ischemic stroke. PATIENTS AND METHODS: Prospectively collected data from consecutive patients with anterior ischemic stroke and AF who underwent carotid imaging from 10 stroke registries were categorized retrospectively according to the degree of stenosis in: no atherosclerosis, stenosis <50%, stenosis ≥50%, and occlusion. Logistic regression analysis was used to identify factors associated with ipsilateral carotid atherosclerosis. RESULTS: Among 2,955 patients with ischemic stroke and AF, carotid atherosclerosis was evident in 1,022 (34.6%) patients, while carotid stenosis ≥50% and occlusion were identified in 204 (6.9%) and 168 (5.7%) patients, respectively. Ipsilateral carotid stenosis ≥50% or occlusion was associated with higher age (OR: 1.15, 95% CI: 1.01-1.32, per decade), previous ischemic stroke or transient ischemic attack (OR: 1.70, 95% CI: 1.29-2.25), peripheral artery disease (OR: 1.85, 95% CI: 1.23-2.78), coronary artery disease (OR: 1.53, 95% CI: 1.16-2.04), and statin treatment on admission (OR: 1.30, 95% CI: 1.01-1.67). Patients with lacunar stroke had a lower likelihood of stenosis ≥50% or occlusion (OR: 0.29, 95% CI: 0.13-0.68). Compared to the absence of atherosclerotic disease, atherosclerosis in one and two arterial beds was associated with the identification of ipsilateral carotid stenosis (OR: 1.49, 95% CI: 1.22-2.98 and OR: 3.18, 95% CI: 1.85-5.49, respectively). CONCLUSION: Among acute ischemic stroke patients with AF, 1 out of 3 had ipsilateral carotid atherosclerosis, and 1 out of 8 had ipsilateral carotid stenosis ≥50% or occlusion. Atherosclerosis in two arterial beds was the most important predictor for the identification of ipsilateral carotid stenosis. Among ischemic stroke patients with AF, carotid atherosclerosis is common, while carotid imaging should not be overlooked, especially in those with coronary or/and peripheral artery disease.

DNA methylation and stroke prognosis: an epigenome-wide association study.

BACKGROUND AND AIMS: Stroke is the leading cause of adult-onset disability. Although clinical factors influence stroke outcome, there is a significant variability among individuals that may be attributed to genetics and epigenetics, including DNA methylation (DNAm). We aimed to study the association between DNAm and stroke prognosis. METHODS AND RESULTS: To that aim, we conducted a two-phase study (discovery-replication and meta-analysis) in Caucasian patients with ischemic stroke from two independent centers (BasicMar [discovery, N = 316] and St. Pau [replication, N = 92]). Functional outcome was assessed using the modified Rankin Scale (mRS) at three months after stroke, being poor outcome defined as mRS > 2. DNAm was determined using the 450K and EPIC BeadChips in whole-blood samples collected within the first 24 h. We searched for differentially methylated positions (DMPs) in 370,344 CpGs, and candidates below p-value < 10-5 were subsequently tested in the replication cohort. We then meta-analyzed DMP results from both cohorts and used them to identify differentially methylated regions (DMRs). After doing the epigenome-wide association study, we found 29 DMPs at p-value < 10-5 and one of them was replicated: cg24391982, annotated to thrombospondin-2 (THBS2) gene (p-valuediscovery = 1.54·10-6; p-valuereplication = 9.17·10-4; p-valuemeta-analysis = 6.39·10-9). Besides, four DMRs were identified in patients with poor outcome annotated to zinc finger protein 57 homolog (ZFP57), Arachidonate 12-Lipoxygenase 12S Type (ALOX12), ABI Family Member 3 (ABI3) and Allantoicase (ALLC) genes (p-value < 1·10-9 in all cases). DISCUSSION: Patients with poor outcome showed a DMP at THBS2 and four DMRs annotated to ZFP57, ALOX12, ABI3 and ALLC genes. This suggests an association between stroke outcome and DNAm, which may help identify new stroke recovery mechanisms.

Acute-to-chronic glycemic ratio as an outcome predictor in ischemic stroke in patients with and without diabetes mellitus.

OBJECTIVE: Elevated plasma glucose levels are common in patients suffering acute ischemic stroke (AIS), and acute hyperglycemia has been defined as an independent determinant of adverse outcomes. The impact of acute-to-chronic glycemic ratio (ACR) has been analyzed in other diseases, but its impact on AIS prognosis remains unclear. The main aim of this study was to assess whether the ACR was associated with a 3-month poor prognosis in patients with AIS. RESEARCH, DESIGN AND METHODS: Retrospective analysis of patients admitted for AIS in Hospital del Mar, Barcelona. To estimate the chronic glucose levels (CGL) we used the formula eCGL= [28.7xHbA1c (%)]-46.7. The ACR (glycemic at admission / eCGL) was calculated for all subjects. Tertile 1 was defined as: 0.28-0.92, tertile 2: 0.92-1.13 and tertile 3: > 1.13. Poor prognosis at 3 months after stroke was defined as mRS score 3-6. RESULTS: 2.774 subjects with AIS diagnosis were included. Age, presence of diabetes, previous disability (mRS), initial severity (NIHSS) and revascularization therapy were associated with poor prognosis (p values < 0.05). For each 0.1 increase in ACR, there was a 7% increase in the risk of presenting a poor outcome. The 3rd ACR tertile was independently associated with a poor prognosis and mortality. In the ROC curves, adding the ACR variable to the classical clinical model did not increase the prediction of AIS prognosis (0.786 vs. 0.781). CONCLUSIONS: ACR was positively associated with a poor prognosis and mortality at 3-months follow-up after AIS. Subjects included in the 3rd ACR tertile presented a higher risk of poor prognosis and mortality. Baseline glucose or ACR did not add predictive value in comparison to only using classical clinical variables.

Blood DNA Methylation Analysis Reveals a Distinctive Epigenetic Signature of Vasospasm in Aneurysmal Subarachnoid Hemorrhage.

Vasospasm is a potentially preventable cause of poor prognosis in patients with aneurysmal subarachnoid hemorrhage (aSAH). Epigenetics might provide insight on its molecular mechanisms. We aimed to analyze the association between differential DNA methylation (DNAm) and development of vasospasm. We conducted an epigenome-wide association study in 282 patients with aSAH admitted to our hospital. DNAm was assessed with the EPIC Illumina chip (> 850 K CpG sites) in whole-blood samples collected at hospital admission. We identified differentially methylated positions (DMPs) at the CpG level using Cox regression models adjusted for potential confounders, and then we used the DMP results to find differentially methylated regions (DMRs) and enriched biological pathways. A total of 145 patients (51%) experienced vasospasm. In the DMP analysis, we identified 31 CpGs associated with vasospasm at p-value < 10-5. One of them (cg26189827) was significant at the genome-wide level (p-value < 10-8), being hypermethylated in patients with vasospasm and annotated to SUGCT gene, mainly expressed in arteries. Region analysis revealed 13 DMRs, some of them annotated to interesting genes such as POU5F1, HLA-DPA1, RUFY1, and CYP1A1. Functional enrichment analysis showed the involvement of biological processes related to immunity, inflammatory response, oxidative stress, endothelial nitric oxide, and apoptosis. Our findings show, for the first time, a distinctive epigenetic signature of vasospasm in aSAH, establishing novel links with essential biological pathways, including inflammation, immune responses, and oxidative stress. Although further validation is required, our results provide a foundation for future research into the complex pathophysiology of vasospasm.

Characteristics and outcomes of cerebral venous thrombosis associated with COVID-19.

INTRODUCTION: Previous reports and meta-analyses derived from small case series reported a mortality rate of up to 40% in patients with coronavirus disease 2019 associated cerebral venous thrombosis (COVID-CVT). We assessed the clinical characteristics and outcomes in an international cohort of patients with COVID-CVT. PATIENTS AND METHODS: This was a registry study of consecutive COVID-CVT patients diagnosed between March 2020 and March 2023. Data collected by the International Cerebral Venous Thrombosis Consortium from patients with CVT diagnosed between 2017 and 2018 served as a comparison. Outcome analyses were adjusted for age and sex. RESULTS: We included 70 patients with COVID-CVT from 23 hospitals in 15 countries and 206 controls from 14 hospitals in 13 countries. The proportion of women was smaller in the COVID-CVT group (50% vs 68%, p < 0.01). A higher proportion of COVID-CVT patients presented with altered mental state (44% vs 25%, p < 0.01), the median thrombus load was higher in COVID-CVT patients (3 [IQR 2-4] vs 2 [1-3], p < 0.01) and the length of hospital stay was longer compared to controls (11 days [IQR 7-20] vs 8 [4-15], p = 0.02). In-hospital mortality did not differ (5/67 [7%, 95% CI 3-16] vs 7/206 [3%, 2-7], aOR 2.6 [95% CI 0.7-9]), nor did the frequency of functional independence after 6 months (modified Rankin Scale 0-2; 45/58 [78%, 95% CI 65-86] vs 161/185 [87%, 81-91], aOR 0.5 [95% CI 0.2-1.02]). CONCLUSION: In contrast to previous studies, the in-hospital mortality rate and functional outcomes during follow-up did not differ between COVID-CVT patients and the pre-COVID-19 controls.

The Role of Epigenetics in Brain Aneurysm and Subarachnoid Hemorrhage: A Comprehensive Review.

This comprehensive review explores the emerging field of epigenetics in intracranial aneurysm (IA) and aneurysmal subarachnoid hemorrhage (aSAH). Despite recent advancements, the high mortality of aSAH needs an understanding of its underlying pathophysiology, where epigenetics plays a crucial role. This review synthesizes the current knowledge, focusing on three primary epigenetic mechanisms: DNA methylation, non-coding RNA (ncRNA), and histone modification in IA and aSAH. While DNA methylation studies are relatively limited, they suggest a significant role in the pathogenesis and prognosis of IA and aSAH, highlighting differentially methylated positions in genes presumably involved in these pathologies. However, methodological limitations, including small sample sizes and a lack of diverse population studies, temper these results. The role of ncRNAs, particularly miRNAs, has been more extensively studied, but there are still few studies focused on histone modifications. Despite methodological challenges and inconsistent findings, these studies underscore the involvement of miRNAs in key pathophysiological processes, including vascular smooth muscle regulation and the inflammatory response. This review emphasizes methodological challenges in epigenetic research, advocating for large-scale epigenome-wide association studies integrating genetic and environmental factors, along with longitudinal studies. Such research could unravel the complex mechanisms behind IA and aSAH, guiding the development of targeted therapeutic approaches.

The influence of epigenetic biological age on key complications and outcomes in aneurysmal subarachnoid haemorrhage.

BACKGROUND: We aimed to investigate the association between DNA-methylation biological age (B-age) calculated as age acceleration (ageAcc) and key aneurysmal subarachnoid haemorrhage (aSAH) complications such as vasospasm, delayed cerebral ischaemia (DCI), poor outcome, and mortality. METHODS: We conducted a prospective study involving 277 patients with aSAH. B-age was determined in whole blood samples using five epigenetic clocks: Hannum's, Horvath's, Levine's and both versions of Zhang's clocks. Age acceleration was calculated as the residual obtained from regressing out the effect of C-age on the mismatch between C-age and B-age. We then tested the association between ageAcc and vasospasm, DCI and 12-month poor outcome (mRS 3-5) and mortality using linear regression models adjusted for confounders. RESULTS: Average C-age was 55.0 years, with 66.8% being female. Vasospasm occurred in 143 cases (51.6%), DCI in 70 (25.3%) and poor outcomes in 99 (35.7%), with a mortality rate of 20.6%. Lower ageAcc was linked to vasospasm in Horvath's and Levine's clocks, whereas increased ageAcc was associated with 12-month mortality in Hannum's clock. No significant differences in ageAcc were found for DCI or poor outcome at 12 months with other clocks. CONCLUSIONS: Our study indicates that B-age is independently associated with vasospasm and 12-month mortality in patients with aSAH. These findings underscore the potential role of epigenetics in understanding the pathophysiology of aSAH-related complications and outcomes.

Flow diverter stents for endovascular treatment of aneurysms: a comparative study of efficacy and safety between FREDX and FRED.

BACKGROUND: The FRED X flow diverter (FREDX), as the second generation in the FRED series, aims to improve the treatment of cerebral aneurysms. This study compares the efficacy and safety of FREDX with its predecessor, FRED. METHODS: This prospective registry included patients treated with FRED and FREDX devices. Efficacy was assessed using digital subtraction angiography with 3D volumetric reconstruction at immediate and 1 year follow-ups. Safety was evaluated by recording complications, analyzed through univariate contrasts, generalized mixed models, and Bayesian network analyses. RESULTS: We treated 287 patients with 385 aneurysms, with 77.9% receiving FRED and 22.1% FREDX. The median age was 55 years (IQR 47-65) and 78.4% were women. The FREDX group showed a higher prevalence of saccular-like aneurysms (70.6% vs 52.7%, P=0.012) and a higher rate of complete occlusion compared with FRED interventions (79.4% vs 59.3%, P=0.022). After adjusting for confounders, these differences represented a 3.04-fold increased likelihood (95% CI 1.44 to 6.41, P=0.003) of achieving complete occlusion at 1 year with FREDX interventions. Regarding safety, two (3.5%) complications (both non-symptomatic) were observed in the FREDX group and 23 (10.4%) in the FRED group (P=0.166). Bayesian network analysis suggested a trend towards fewer complications for FREDX, with a median reduction of 5.5% in the posterior distribution of the prevalence of complications compared with FRED interventions. CONCLUSIONS: The FREDX device shows improved complete occlusion rates at 1 year compared with the FRED device while maintaining a favourable safety profile, indicating its potential advantage in the treatment of cerebral aneurysms.

Long-term effectiveness and tolerability of galcanezumab in patients with migraine excluded from clinical trials: real world evidence of 1055 patients with 1 year follow-up from the Galca-Only registry.

BACKGROUND: Galcanezumab has shown efficacy and effectiveness in the treatment of episodic and chronic migraine (CM), however, the population represented in randomized clinical trials (RCTs) differs from the population observed in real-world setting. To describe the long-term effectiveness and tolerability of galcanezumab in clinical practice in patients excluded from RCTs. METHODS: Multicenter prospective cohort study of consecutive patients with chronic and high-frequency episodic migraine (HFEM) with prior failure to three or more migraine preventive drugs, treated with galcanezumab and followed up for 12 months. RESULTS: We enrolled 1055 patients, aged 50 (IQR: 42-58), 82.9% female, 76.4% chronic migraine, 69% with at least one exclusion criteria for RCTs, including age > 65 (n = 121), concomitant use of onabotulinumtoxinA (n = 185), daily headache at baseline (n = 347), chronic painful syndromes (n = 206), fibromyalgia (n = 101) or treatment resistance (n = 957). The median number of prior preventive treatments was 4 (IQR: 3-5). The retention rate was 90.8%, 76.8% and 71.4% at 3, 6 and 12 months. The main reasons for treatment discontinuation were lack of effectiveness (21.1%) and inadequate tolerability (6.6%). The 30%, 50% and 75% responder rates were 62.6%, 49.8% and 24.2% between weeks 8-12; 60.9%, 48.8% and 24.6% between weeks 20-24; and 59.7%, 48.3% and 24.6% between weeks 44-48. Daily headache at baseline (OR: 0.619; 95%CI: 0.469-0.817) and patient's age (OR: 1.016; 95%CI: 1.005-1.026) were associated with 50% response at weeks 20-24. The variables that were associated with a higher reduction of headache days between weeks 20-24 were patient's age (0.068; 95% CI: 0.018-0.119) and headache days per month at baseline (0.451; 95% CI: 0.319-0.583), while psychiatric comorbidity (-1.587; 95% CI: -2.626-0.538) and daily headache at baseline (-2.718; 95% CI: -4.58-0.869) were associated with fewer reduction in the number of headache days between weeks 20-24. CONCLUSION: This study provides class III evidence of effectiveness and tolerability of galcanezumab in patients with HFEM and CM with comorbidities that would result in exclusion of the pivotal RCTs. Nonetheless, the clinical results over a 12-month period were similar to the efficacy observed in randomized controlled trials. Few patients discontinued the drug due to inadequate tolerability.

Treatment of COVID-19 during the Acute Phase in Hospitalized Patients Decreases Post-Acute Sequelae of COVID-19.

BACKGROUND: The post-acute sequelae of SARS-CoV-2 (PASC) infection have caused a significant impact on our health system, but there is limited evidence of approved drugs focused on its prevention. Our objective was to identify risk factors that can determine the presence of PASC, with special attention to the treatment received in the acute phase, and to describe the profile of persistent symptoms in a multidisciplinary Post-Coronavirus Disease-19 (COVID-19) Unit. METHODS: This one-year prospective observational study included patients following an acute COVID-19 infection, irrespective of whether they required hospital admission. A standardized symptom questionnaire and blood sampling were performed at the first follow-up visit, and demographic and clinical electronic data were collected. We compared subjects with PASC with those who had fully recovered. Multivariate logistic regression was performed to identify factors associated with PASC in hospitalized patients, and Kaplan-Meier curves were used to assess duration of symptoms according to disease severity and treatments received in the acute phase. RESULTS: 1966 patients were evaluated; 1081 had mild disease, 542 moderate and 343 severe; around one third of the subjects had PASC, and were more frequently female, with obesity, asthma, and eosinophilia during acute COVID-19 disease. Patients who received treatment with dexamethasone and remdesivir during the course of the acute illness showed a lower median duration of symptoms, compared with those who received none of these treatments. CONCLUSION: Treatment with dexamethasone and/or remdesivir may be useful to reduce the impact of PASC secondary to SARS-CoV-2 infection. In addition, we identified female gender, obesity, asthma, and disease severity as risk factors for having PASC.

Factors associated with migraine aura mimicking stroke in code stroke.

INTRODUCTION: Migraine with aura (MA) is a frequent stroke simulator that can lead to erroneous diagnosis and subsequent unnecessary acute or secondary prevention treatments. We analyzed clinical and laboratory data of migraine with aura and ischemic stroke patients to detect differences that could help in the diagnosis. METHODS: Retrospective analysis of a consecutive register of code strokes between January 2005 and June 2020. Diagnosis of ischemic stroke or MA was collected. Multivariable logistic regression analyses were performed to test associations between clinical and blood data with ischemic stroke. RESULTS: Of 3140 code strokes, 2424 (77.2%) were ischemic strokes and 34 (1.1%) were MA. Migraine cases were younger, more frequently females and with lower prevalence of vascular risk factors. Initial NIHSS was lower in MA cases, but no differences were seen in fibrinolysis rate (30%). Blood test showed lower levels of glucose, D-dimer, and fibrinogen in MA cases. Multivariable model showed and independent association for ischemic stroke with age [OR, (95%CI): 1.09, (1.07-1.12, p < 0.001], male sex [OR, (95%CI): 4.47, (3.80-5.13), p < 0.001], initial NIHSS [OR, (95%CI): 1.21, (1.07-1.34), p < 0.01], and fibrinogen levels [OR, (95%CI): 1.01, (1.00-1.01), p < 0.05]. A model including sex male OR: 3.55 [2.882; 4.598], p < 0.001, and cutoff points (age > 65, OR: 7.953 [7.256; 8.649], p < 0.001, NIHSS > 6, OR: 3.740 [2.882; 4.598], p < 0.01, and fibrinogen > 400 mg/dL, OR: 2.988 [2.290; 3.686], p < 0.01) showed a good global discrimination capability AUC = 0.89 (95%CI: 0.88-0.94). CONCLUSIONS: In code stroke, a model including age, sex, NIHSS, and fibrinogen showed a good discrimination capability to differentiate between MA and Ischemic stroke. Whether these variables can be implemented in a diagnostic rule should be tested in future studies.

Machine Learning Approximations to Predict Epigenetic Age Acceleration in Stroke Patients.

Age acceleration (Age-A) is a useful tool that is able to predict a broad range of health outcomes. It is necessary to determine DNA methylation levels to estimate it, and it is known that Age-A is influenced by environmental, lifestyle, and vascular risk factors (VRF). The aim of this study is to estimate the contribution of these easily measurable factors to Age-A in patients with cerebrovascular disease (CVD), using different machine learning (ML) approximations, and try to find a more accessible model able to predict Age-A. We studied a CVD cohort of 952 patients with information about VRF, lifestyle habits, and target organ damage. We estimated Age-A using Hannum's epigenetic clock, and trained six different models to predict Age-A: a conventional linear regression model, four ML models (elastic net regression (EN), K-Nearest neighbors, random forest, and support vector machine models), and one deep learning approximation (multilayer perceptron (MLP) model). The best-performing models were EN and MLP; although, the predictive capability was modest (R2 0.358 and 0.378, respectively). In conclusion, our results support the influence of these factors on Age-A; although, they were not enough to explain most of its variability.

Intracranial Aneurysm Classifier Using Phenotypic Factors: An International Pooled Analysis.

Intracranial aneurysms (IAs) are usually asymptomatic with a low risk of rupture, but consequences of aneurysmal subarachnoid hemorrhage (aSAH) are severe. Identifying IAs at risk of rupture has important clinical and socio-economic consequences. The goal of this study was to assess the effect of patient and IA characteristics on the likelihood of IA being diagnosed incidentally versus ruptured. Patients were recruited at 21 international centers. Seven phenotypic patient characteristics and three IA characteristics were recorded. The analyzed cohort included 7992 patients. Multivariate analysis demonstrated that: (1) IA location is the strongest factor associated with IA rupture status at diagnosis; (2) Risk factor awareness (hypertension, smoking) increases the likelihood of being diagnosed with unruptured IA; (3) Patients with ruptured IAs in high-risk locations tend to be older, and their IAs are smaller; (4) Smokers with ruptured IAs tend to be younger, and their IAs are larger; (5) Female patients with ruptured IAs tend to be older, and their IAs are smaller; (6) IA size and age at rupture correlate. The assessment of associations regarding patient and IA characteristics with IA rupture allows us to refine IA disease models and provide data to develop risk instruments for clinicians to support personalized decision-making.

Outcomes of Cerebral Venous Thrombosis due to Vaccine-Induced Immune Thrombotic Thrombocytopenia After the Acute Phase.

BACKGROUND: Cerebral venous thrombosis (CVT) due to vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe condition, with high in-hospital mortality rates. Here, we report clinical outcomes of patients with CVT-VITT after SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccination who survived initial hospitalization. METHODS: We used data from an international registry of patients who developed CVT within 28 days of SARS-CoV-2 vaccination, collected until February 10, 2022. VITT diagnosis was classified based on the Pavord criteria. Outcomes were mortality, functional independence (modified Rankin Scale score 0-2), VITT relapse, new thrombosis, and bleeding events (all after discharge from initial hospitalization). RESULTS: Of 107 CVT-VITT cases, 43 (40%) died during initial hospitalization. Of the remaining 64 patients, follow-up data were available for 60 (94%) patients (37 definite VITT, 9 probable VITT, and 14 possible VITT). Median age was 40 years and 45/60 (75%) patients were women. Median follow-up time was 150 days (interquartile range, 94-194). Two patients died during follow-up (3% [95% CI, 1%-11%). Functional independence was achieved by 53/60 (88% [95% CI, 78%-94%]) patients. No new venous or arterial thrombotic events were reported. One patient developed a major bleeding during follow-up (fatal intracerebral bleed). CONCLUSIONS: In contrast to the high mortality of CVT-VITT in the acute phase, mortality among patients who survived the initial hospitalization was low, new thrombotic events did not occur, and bleeding events were rare. Approximately 9 out of 10 CVT-VITT patients who survived the acute phase were functionally independent at follow-up.

Long-term vascular events after subarachnoid hemorrhage.

BACKGROUND: Spontaneous subarachnoid hemorrhage (SAH) long-term risk is not well known. Our aims are: describing long-term vascular event (VE) incidence rates in SAH survivors; describing VE: ischemic and/or hemorrhagic; identifying independent association of factors related to VE; and analyzing the usefulness of factors to increase predictive ability. METHODS: A prospective cohort study of consecutive patients admitted to Hospital del Mar with a diagnosis of SAH (n = 566) between January 2007 and January 2020 was carried out. They were followed up until January 2021. The study endpoint was a new VE in the follow-up. We calculated both incidence rates and cumulative rates at 5 years. Cox regression survival models including vascular risk factors with and without specific data of SAH disease were developed. We analyzed ROC curves of all multivariate models. RESULTS: The analyzed cohort included 423 non-fatal SAH cases. Total patient-years were 2468.16 years. The average follow-up was 70.03 ± 43.14; range: 1-180 months. There were 49 VE detected in 47 patients, as 2 of them had more than 1 VE. Incidence rate was 0.020 events_per_patient/year, cumulative incidence at 5 years was 11.11%. The more frequent VE that we found were cerebrovascular (28/49), mainly ischemic (21/28). Disability after SAH and the presence of multiple aneurysms were independently associated with a VE risk and improved the predictive capacity of multivariate models (AUC 0.679 vs 0.764; p = 0.0062). CONCLUSIONS: We reported a low vascular risk after SAH. We have shown the usefulness of SAH factors to identify patients with a higher risk of VE.

Management of Cerebral Venous Thrombosis Due to Adenoviral COVID-19 Vaccination.

OBJECTIVE: Cerebral venous thrombosis (CVT) caused by vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare adverse effect of adenovirus-based severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccines. In March 2021, after autoimmune pathogenesis of VITT was discovered, treatment recommendations were developed. These comprised immunomodulation, non-heparin anticoagulants, and avoidance of platelet transfusion. The aim of this study was to evaluate adherence to these recommendations and its association with mortality. METHODS: We used data from an international prospective registry of patients with CVT after the adenovirus-based SARS-CoV-2 vaccination. We analyzed possible, probable, or definite VITT-CVT cases included until January 18, 2022. Immunomodulation entailed administration of intravenous immunoglobulins and/or plasmapheresis. RESULTS: Ninety-nine patients with VITT-CVT from 71 hospitals in 17 countries were analyzed. Five of 38 (13%), 11 of 24 (46%), and 28 of 37 (76%) of the patients diagnosed in March, April, and from May onward, respectively, were treated in-line with VITT recommendations (p < 0.001). Overall, treatment according to recommendations had no statistically significant influence on mortality (14/44 [32%] vs 29/55 [52%], adjusted odds ratio [OR] = 0.43, 95% confidence interval [CI] = 0.16-1.19). However, patients who received immunomodulation had lower mortality (19/65 [29%] vs 24/34 [70%], adjusted OR = 0.19, 95% CI = 0.06-0.58). Treatment with non-heparin anticoagulants instead of heparins was not associated with lower mortality (17/51 [33%] vs 13/35 [37%], adjusted OR = 0.70, 95% CI = 0.24-2.04). Mortality was also not significantly influenced by platelet transfusion (17/27 [63%] vs 26/72 [36%], adjusted OR = 2.19, 95% CI = 0.74-6.54). CONCLUSIONS: In patients with VITT-CVT, adherence to VITT treatment recommendations improved over time. Immunomodulation seems crucial for reducing mortality of VITT-CVT. ANN NEUROL 2022;92:562-573.