Search

BACKGROUND The effect of early as compared with later initiation of direct oral anticoagulants (DOACs) in persons with atrial fibrillation who have had an acute ischemic stroke is unclear. METHODS We performed an investigator-initiated, open-label trial at 103 sites in 15 countries. Participants were randomly assigned in a 1:1 ratio to early anticoagulation (within 48 hours after a minor or moderate stroke or on day 6 or 7 after a major stroke) or later anticoagulation (day 3 or 4 after a minor stroke, day 6 or 7 after a moderate stroke, or day 12, 13, or 14 after a major stroke). Assessors were unaware of the trial-group assignments. The primary outcome was a composite of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death within 30 days after randomization. Secondary outcomes included the components of the composite primary outcome at 30 and 90 days. RESULTS Of 2013 participants (37% with minor stroke, 40% with moderate stroke, and 23% with major stroke), 1006 were assigned to early anticoagulation and 1007 to later anticoagulation. A primary-outcome event occurred in 29 participants (2.9%) in the early-treatment group and 41 participants (4.1%) in the later-treatment group (risk difference, -1.18 percentage points; 95% confidence interval [CI], -2.84 to 0.47) by 30 days. Recurrent ischemic stroke occurred in 14 participants (1.4%) in the early-treatment group and 25 participants (2.5%) in the later-treatment group (odds ratio, 0.57; 95% CI, 0.29 to 1.07) by 30 days and in 18 participants (1.9%) and 30 participants (3.1%), respectively, by 90 days (odds ratio, 0.60; 95% CI, 0.33 to 1.06). Symptomatic intracranial hemorrhage occurred in 2 participants (0.2%) in both groups by 30 days. CONCLUSIONS In this trial, the incidence of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death at 30 days was estimated to range from 2.8 percentage points lower to 0.5 percentage points higher (based on the 95% confidence interval) with early than with later use of DOACs. (Funded by the Swiss National Science Foundation and others; ELAN ClinicalTrials.gov number, NCT03148457.) [ABSTRACT FROM AUTHOR]

Importance: Cerebral small vessel disease (SVD) is associated with various cerebrovascular outcomes, but data on sex differences in SVD are scarce., Objective: To investigate whether the frequency, severity, and distribution of cerebral microbleeds (CMB), other SVD markers on magnetic resonance imaging (MRI), and outcomes differ by sex., Design, Setting, and Participants: This cohort study used pooled individual patient data from the Microbleeds International Collaborative Network, including patients from 38 prospective cohort studies in 18 countries between 2000 and 2018, with clinical follow-up of at least 3 months (up to 5 years). Participants included patients with acute ischemic stroke or transient ischemic attack with available brain MRI. Data were analyzed from April to December 2023., Main Outcomes and Measures: Outcomes of interest were presence of CMB, lacunes, and severe white matter hyperintensities determined on MRI. Additionally, mortality, recurrent ischemic stroke, and intracranial hemorrhage during follow-up were assessed. Multivariable random-effects logistic regression models, Cox regression, and competing risk regression models were used to investigate sex differences in individual SVD markers, risk of recurrent cerebrovascular events, and death., Results: A total of 20 314 patients (mean [SD] age, 70.1 [12.7] years; 11 721 [57.7%] male) were included, of whom 5649 (27.8%) had CMB. CMB were more frequent in male patients, and this was consistent throughout different age groups, locations, and in multivariable models (female vs male adjusted odds ratio [aOR], 0.86; 95% CI, 0.80-0.92; P < .001). Female patients had fewer lacunes (aOR, 0.82; 95% CI, 0.74-0.90; P < .001) but a higher prevalence of severe white matter hyperintensities (aOR, 1.10; 95% CI, 1.01-1.20; P = .04) compared with male patients. A total of 2419 patients (11.9%) died during a median (IQR) follow-up of 1.4 (0.7-2.5) years. CMB presence was associated with a higher risk of mortality in female patients (hazard ratio, 1.15; 95% CI, 1.02-1.31), but not male patients (hazard ratio, 0.95; 95% CI, 0.84-1.07) (P for interaction = .01). A total of 1113 patients (5.5%) had recurrent ischemic stroke, and 189 patients (0.9%) had recurrent intracranial hemorrhage, with no sex differences., Conclusions and Relevance: This cohort study using pooled individual patient data found varying frequencies of individual SVD markers between female and male patients, indicating potential pathophysiological differences in manifestation and severity of SVD. Further research addressing differences in pathomechanisms and outcomes of SVD between female and male patients is required.

Objectives: Cerebral amyloid angiopathy (CAA)-associated lobar intracerebral hemorrhage (ICH) has a high risk of recurrence, but the underlying mechanisms remain uncertain. We, therefore, aimed to characterize patterns of recurrent ICH., Methods: We investigated early recurrent ICH (≥1 recurrent ICH event within 90 days of the index event) and ICH clusters (≥2 ICH events within 90 days at any time point) in 2 large cohorts of consecutive patients with first-ever ICH and available MRI., Results: In 682 included patients (median age 68 years, 40.3% female, median follow-up time 4.1 years), 18 (2.6%) had an early recurrent ICH, which was associated with higher age and CAA. In patients with probable CAA, the risk of early recurrent ICH was increased 5-fold within the first 3 months compared with during months 4-12 (hazard ratio 5.41, 95% CI 2.18-13.4) while no significant difference was observed in patients without CAA. In patients with an ICH cluster, we observed spatial clustering (recurrent ICH within close proximity of index ICH in 63.0%) and a tendency for multiple sequential hemorrhages (≥3 ICH foci within 3 months in 44.4%)., Discussion: Our data provide evidence of both temporal and spatial clustering of ICH in CAA, suggesting a transient and localized active bleeding-prone process.

Background: Intravenous thrombolysis (IVT) is an approved treatment for patients with acute ischemic stroke irrespective of sex. However, the current literature on sex differences in functional outcomes following IVT is inconsistent. So far, a number of studies-including a previous analysis based on data from the Austrian Stroke Unit Registry (ASUR)-detected significant sex-related differences in functional outcome, while others did not report any differences between women and men. In addition, currently there is a lack of data on how sex-related differences evolve over time., Aims: To assess time trends of sex-related differences in functional outcome of ischemic stroke in a large nationwide cohort and to investigate associations of patient characteristics with functional outcome post thrombolysis in women and men. These data will offer crucial insights into whether sex differences in functional outcome persist despite the large advances in acute stroke treatment., Methods: We analyzed retrospective data of consecutive patients with acute ischemic stroke treated with IVT in 39 stroke centers contributing to the ASUR between 2006 and 2021. We included patients over 18 years of age diagnosed with an acute ischemic stroke who received IVT and with available data on functional outcome at 3 months after treatment. The primary outcome parameter was favorable functional outcome (modified Rankin Scale (mRS) of 0-2) at 3 months. Multivariable logistic regression analysis was performed in the overall population and stratified by sex to assess associations of baseline characteristics with functional outcome., Results: Among 11,840 patients receiving IVT, 2489 of 5503 (45.4%) women achieved favorable functional outcome compared to 3787 of 6337 (59.8%) men. Overall, female sex was a statistically significant predictor of functional outcome after thrombolysis, but additional predictors of outcome differed between women and men. Female sex was independently associated with decreased chances of achieving functional independency (adjusted odds ratio (adjOR) = 0.87, 95% confidence interval (CI) = 0.79-0.96, p = 0.005) and we detected a statistically significant improvement in functional outcome over time only in men (year of treatment, adjOR (per year) = 1.04, 95% CI = 1.02-1.06, p < 0.001) but not in women (adjOR (per year) = 1.01, 95% CI = 0.99-1.03, p = 0.280). Hypertension, smoking, and longer or unknown onset-to-door times were statistically significant predictors of outcome only in male patients, whereas atrial fibrillation, prior myocardial infarction, and longer door-to-needle times were significantly associated with outcome only in women., Conclusions: Sex differences in functional outcome after IVT for acute ischemic stroke are persisting over the past years. Results of our analysis can increase awareness and a resulting focus on sex differences in predictors of outcome could be helpful in mitigating these differences in the future by supporting a more individualized patient care in clinical routine. Follow-up analyses are needed to assess this potential impact and its effect in the future., Data Access Statement: Data from the Austrian Stroke Unit Registry can only be accessed by the employed statistician (D.M.), access inquiries have to be addressed to the registry's academic review board., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: M.M. reports honoraria from Boehringer-Ingelheim. M.K. reports honoraria from Daiichi Sankyo, Boehringer-Ingelheim, Sanofi-Aventis; travel grants from Pfizer, the Austrian Stroke Society and the European Stroke Organization; and grants from the Austrian National Bank Anniversary Fund, the Austrian Research Promotaion Agency, and VASCage. S.K. reports grants from VASCage. The remaining authors report no disclosures.

Delirium is a common complication in acute stroke patients, occurring in 15-35% of all stroke unit admissions and is associated with prolonged hospital stay and a poor post-stroke prognosis. Managing delirium in acute stroke patients necessitates an intensive and multiprofessional therapeutic approach, placing a significant burden on healthcare staff. However, dedicated practical recommendations for delirium management developed for the population of acute stroke patients are lacking. For this purpose, the Austrian Stroke Society, in cooperation with the Austrian Society of Neurology, the Austrian Society of Neurorehabilitation, and the Austrian Society of Psychiatry, Psychotherapy, and Psychosomatics has formulated an evidence-based position paper addressing the management of delirium in acute stroke patients. The paper outlines practical recommendations on the three pillars of care in stroke patients with delirium: (a) Key aspects of delirium prevention including stroke-specific delirium risk factors and delirium prediction scores are described. Moreover, a non-pharmacological delirium prevention bundle is presented. (b) The paper provides recommendations on timing and frequency of delirium screening to ensure early diagnosis of delirium in acute stroke patients. Moreover, it reports on the use of different delirium screening tools in stroke populations. (c) An overview of non-pharmacological and pharmacological treatment strategies in patients with delirium and acute stroke is presented and summarized as key recommendation statements., (© The Author(s), 2024.)

Background: Recent small subcortical infarcts (RSSI) are the neuroimaging hallmark feature of small vessel disease (SVD)-related acute lacunar stroke. Long-term data on recurrent cerebrovascular events including their aetiology after RSSI are scarce., Patients and Methods: This retrospective study included all consecutive ischaemic stroke patients with an MRI-confirmed RSSI (in the supply area of a small single brain artery) at University Hospital Graz between 2008 and 2013. We investigated associations between clinical and SVD features on MRI (STRIVE criteria) and recurrent cerebrovascular events, using multivariable Cox regression adjusted for age, sex, vascular risk factors and MRI parameters., Results: We analysed 332 consecutive patients (mean age 68 years, 36% women; median follow-up time 12 years). A recurrent ischaemic cerebrovascular event occurred in 70 patients (21.1%; 54 ischaemic strokes, 22 transient ischaemic attacks) and was mainly attributed to SVD (68%). 26 patients (7.8%) developed intracranial haemorrhage. In multivariable analysis, diabetes (HR 2.43, 95% CI 1.44-3.88), severe white matter hyperintensities (HR 1.97, 95% CI 1.14-3.41), and cerebral microbleeds (HR 1.89, 95% CI 1.32-3.14) on baseline MRI were related to recurrent ischaemic stroke/TIA, while presence of cerebral microbleeds increased the risk for intracranial haemorrhage (HR 3.25, 95% CI 1.39-7.59). A widely used SVD summary score indicated high risks of recurrent ischaemic (HR 1.22, 95% CI 1.01-1.49) and haemorrhagic cerebrovascular events (HR 1.57, 95% CI 1.11-2.22)., Conclusion: Patients with RSSI have a substantial risk for recurrent cerebrovascular events-particularly those with coexisting chronic SVD features. Recurrent events are mainly related to SVD again., (© 2024. The Author(s).)

Background and Objectives: Chronic kidney disease (CKD) may be associated with the pathogenesis and phenotype of cerebral small vessel disease (SVD), which is the commonest cause of intracerebral hemorrhage (ICH). The purpose of this study was to investigate the associations of CKD with ICH neuroimaging phenotype, volume, and location, total burden of small vessel disease, and its individual components., Methods: In 2 cohorts of consecutive patients with ICH evaluated with MRI, we investigated the frequency and severity of CKD based on established Kidney Disease Improving Global Outcomes criteria, requiring estimated glomerular filtration rate (eGFR) measurements <60 mL/min/1.73 2 ≥ 3 months apart to define CKD. MRI scans were rated for ICH neuroimaging phenotype (arteriolosclerosis, cerebral amyloid angiopathy, mixed location SVD, or cryptogenic ICH) and the presence of markers of SVD (white matter hyperintensities [WMHs], cerebral microbleeds [CMBs], lacunes, and enlarged perivascular spaces, defined according to the STandards for ReportIng Vascular changes on nEuroimaging criteria). We used multinomial, binomial logistic, and ordinal logistic regression models adjusted for age, sex, hypertension, and diabetes to account for possible confounding caused by shared risk factors of CKD and SVD., Results: Of 875 patients (mean age 66 years, 42% female), 146 (16.7%) had CKD. After adjusting for age, sex, and comorbidities, patients with CKD had higher rates of mixed SVD than those with eGFR >60 (relative risk ratio 2.39, 95% CI 1.16-4.94, p = 0.019). Severe WMHs, deep microbleeds, and lacunes were more frequent in patients with CKD, as was a higher overall SVD burden score (odds ratio 1.83 for each point on the ordinal scale, 95% CI 1.31-2.56, p < 0.001). Patients with eGFR ≤30 had more CMBs (median 7 [interquartile range 1-23] vs 2 [0-8] for those with eGFR >30, p = 0.007)., Discussion: In patients with ICH, CKD was associated with SVD burden, a mixed SVD phenotype, and markers of arteriolosclerosis. Our findings indicate that CKD might independently contribute to the pathogenesis of arteriolosclerosis and mixed SVD, although we could not definitively account for the severity of shared risk factors. Longitudinal and experimental studies are, therefore, needed to investigate causal associations. Nevertheless, stroke clinicians should be aware of CKD as a potentially independent and modifiable risk factor of SVD.

Background and Objectives: We recently developed a model (PROCEED) that predicts the occurrence of persistent perfusion deficit (PPD) at 24 hours in patients with incomplete angiographic reperfusion after thrombectomy. This study aims to externally validate the PROCEED model using prospectively acquired multicenter data., Methods: Individual patient data for external validation were obtained from the Endovascular Therapy for Ischemic Stroke with Perfusion-Imaging Selection, Tenecteplase versus Alteplase Before Endovascular Therapy for Ischemic Stroke part 1 and 2 trials, and a prospective cohort of the Medical University of Graz. The model's primary outcome was the occurrence of PPD, defined as a focal, wedge-shaped perfusion delay on 24-hour follow-up perfusion imaging that corresponds to the capillary phase deficit on last angiographic series in patients with

Background: Knowledge about factors that are associated with post-stroke cognitive outcome is important to identify patients with high risk for impairment. We therefore investigated the associations of white matter integrity and functional connectivity (FC) within the brain's default-mode network (DMN) in acute stroke patients with cognitive outcome three months post-stroke., Methods: Patients aged between 18 and 85 years with an acute symptomatic MRI-proven unilateral ischemic middle cerebral artery infarction, who had received reperfusion therapy, were invited to participate in this longitudinal study. All patients underwent brain MRI within 24-72 h after symptom onset, and participated in a neuropsychological assessment three months post-stroke. We performed hierarchical regression analyses to explore the incremental value of baseline white matter integrity and FC beyond demographic, clinical, and macrostructural information for cognitive outcome., Results: The study cohort comprised 34 patients (mean age: 64 ± 12 years, 35% female). The initial median National Institutes of Health Stroke Scale (NIHSS) score was 10, and significantly improved three months post-stroke to a median NIHSS = 1 (p < .001). Nonetheless, 50% of patients showed cognitive impairment three months post-stroke. FC of the non-lesioned anterior cingulate cortex of the affected hemisphere explained 15% of incremental variance for processing speed (p = .007), and fractional anisotropy of the non-lesioned cingulum of the affected hemisphere explained 13% of incremental variance for cognitive flexibility (p = .033)., Conclusions: White matter integrity and functional MRI markers of the DMN in acute stroke explain incremental variance for post-stroke cognitive outcome beyond demographic, clinical, and macrostructural information., Competing Interests: Declaration of competing interest The authors declare no financial or other conflicts of interest that relate to the research covered in this article., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Importance: Whether infarct size modifies the treatment effect of early vs late direct oral anticoagulant (DOAC) initiation in people with ischemic stroke and atrial fibrillation is unknown., Objective: To assess whether infarct size modifies the safety and efficacy of early vs late DOAC initiation., Design, Setting, and Participants: Post hoc analysis of participants from the multinational (>100 sites in 15 countries) randomized clinical Early Versus Later Anticoagulation for Stroke With Atrial Fibrillation (ELAN) trial who had (1) acute ischemic stroke, (2) atrial fibrillation, and (3) brain imaging available before randomization. The ELAN trial was conducted between October 2017 and December 2022. Data were analyzed from October to December 2023 for this post hoc analysis., Intervention: Early vs late DOAC initiation after ischemic stroke. Early DOAC initiation was within 48 hours for minor or moderate stroke or on days 6 to 7 for major stroke; late DOAC initiation was on days 3 to 4 for minor stroke, days 6 to 7 for moderate stroke, and days 12 to 14 for major stroke., Main Outcomes and Measures: The primary outcome was a composite of recurrent ischemic stroke, symptomatic intracranial hemorrhage, extracranial bleeding, systemic embolism, or vascular death within 30 days. The outcome was assessed according to infarct size (minor, moderate, or major) using odds ratios and risk differences between treatment arms. Interrater reliability for infarct size between the core laboratory and local raters was assessed, and whether this modified the estimated treatment effects was also examined., Results: A total of 1962 of the original 2013 participants (909 [46.3%] female; median [IQR] age, 77 [70-84] years) were included. The primary outcome occurred in 10 of 371 participants (2.7%) with early DOAC initiation vs 11 of 364 (3.0%) with late DOAC initiation among those with minor stroke (odds ratio [OR], 0.89; 95% CI, 0.38-2.10); in 11 of 388 (2.8%) with early DOAC initiation vs 14 of 392 (3.6%) with late DOAC initiation among those with moderate stroke (OR, 0.80; 95% CI, 0.35-1.74); and in 8 of 219 (3.7%) with early DOAC initiation vs 16 of 228 (7.0%) with late DOAC initiation among those with major stroke (OR, 0.52; 95% CI, 0.21-1.18). The 95% CI for the estimated risk difference of the primary outcome in early anticoagulation was -2.78% to 2.12% for minor stroke, -3.23% to 1.76% for moderate stroke, and -7.49% to 0.81% for major stroke. There was no significant treatment interaction for the primary outcome. For infarct size, interrater reliability was moderate (κ = 0.675; 95% CI, 0.647-0.702) for local vs core laboratory raters and strong (κ = 0.875; 95% CI, 0.855-0.894) between core laboratory raters., Conclusions and Relevance: The treatment effect of early DOAC initiation did not differ in people with minor, moderate, or major stroke assessed by brain imaging. Early treatment was not associated with a higher rate of adverse events, especially symptomatic intracranial hemorrhage, for any infarct size, including major stroke., Trial Registration: ClinicalTrials.gov Identifier: NCT03148457.

Introduction: To date, risk assessment of suffering ischemic and hemorrhagic stroke in individuals under oral anticoagulation (OAC) is limited to hospital-based cohorts and patients with atrial fibrillation., Patients and Methods: Through the combination of three individual datasets, (1) the population-based Tyrolean Stroke Pathway database, prospectively documenting all (unselected) stroke patients in the entire federal state of the Tyrol and (2) nation-wide prescription data, detailing each reimbursed prescription in Austria as well as (3) the Austrian Stroke Unit Registry, a nation-wide registry comprising data on all patients admitted to any of the 38 stroke units in Austria, we assessed risk of stroke in patients with prior oral anticoagulation and compared characteristics of patients taking direct oral anticoagulants and Vitamin-K-Antagonists., Results: In Austria, oral anticoagulant prescription reimbursements increased from 292,475 in 2015 to 389,407 in 2021. In the Tyrol, prior oral anticoagulation treatment was evident in 586 of 3861 (15.2%) patients with ischemic and 131 of 523 (25.0%) with hemorrhagic stroke, with 20% and 35% of those stroke patients respectively having prior oral anticoagulation due to other indications than non-valvular atrial fibrillation. Considering prescription rates, treatment with direct oral anticoagulants was associated with a reduced stroke risk compared to Vitamin-K-Antagonists, especially in ischemic (1.05% vs 0.62%; RR 0.59, p  < 0.001) but also in hemorrhagic stroke, even if less pronounced (0.21% vs 0.14%; RR 0.68, p  = 0.06). In Austria, prior intake of direct oral anticoagulants was associated with lower risk of suffering acute large vessel occlusion stroke (RR 0.79, p  = 0.003)., Discussion and Conclusions: One in seven patients suffering ischemic and one in four suffering hemorrhagic stroke had prior oral anticoagulation treatment. Both ischemic and hemorrhagic strokes are less frequent in those with direct oral anticoagulant intake compared to those taking Vitamin-K-Antagonists. Establishment of clear standard operating procedures on how to best care for acute stroke patients with oral anticoagulation is essential., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Whether hemorrhagic transformation (HT) modifies the treatment effect of early versus late initiation of direct oral anticoagulation (DOAC) in people with ischemic stroke and atrial fibrillation is unknown., Methods: This is a post-hoc analysis of the ELAN trial. The primary outcome was a composite of recurrent ischemic stroke, symptomatic intracranial hemorrhage (sICH), major extracranial bleeding, systemic embolism, or vascular death within 30 days. Secondary outcomes were the individual components, 30- and 90-day functional outcome. We estimated outcomes based on HT, subclassified as hemorrhagic infarction (HI) or parenchymal hemorrhage (PH) on pre-randomization imaging (core-lab rating) using adjusted risk differences (aRD) between treatment arms., Results: Overall, 247/1970 (12.5%) participants had HT (114 HI 1, 77 HI 2, 34 PH 1, 22 PH 2). For the primary outcome, the estimated aRD (early versus late) was -2.2% (-7.8 to 3.5%) in people with HT (HI: -4.7%, -10.8 to 1.4%; PH: 6.1%, -8.4 to 20.7%), and -0.9% (-2.6 to 0.8%) in people without. Numbers of sICH were identical in people with and without HT. With early treatment, the estimated aRD for poor 90-day functional outcome (mRS 3-6) was 11.4% (-0.9 to 23.7%) in participants with HT (HI: 7.2%, -6.6 to 21.0%; PH: 25.1%, 0.2 to 50.0%), and -2.6% (-7.1 to 1.8%) in people without HT., Conclusions: We found no evidence of major treatment effect heterogeneity or safety concerns with early versus late DOAC initiation in people with and without HT. However, early DOAC initiation may worsen functional outcomes in people with PH.

Neurofilament proteins have been validated as specific body fluid biomarkers of neuro-axonal injury. The advent of highly sensitive analytical platforms that enable reliable quantification of neurofilaments in blood samples and simplify longitudinal follow-up has paved the way for the development of neurofilaments as a biomarker in clinical practice. Potential applications include assessment of disease activity, monitoring of treatment responses, and determining prognosis in many acute and chronic neurological disorders as well as their use as an outcome measure in trials of novel therapies. Progress has now moved the measurement of neurofilaments to the doorstep of routine clinical practice for the evaluation of individuals. In this Review, we first outline current knowledge on the structure and function of neurofilaments. We then discuss analytical and statistical approaches and challenges in determining neurofilament levels in different clinical contexts and assess the implications of neurofilament light chain (NfL) levels in normal ageing and the confounding factors that need to be considered when interpreting NfL measures. In addition, we summarize the current value and potential clinical applications of neurofilaments as a biomarker of neuro-axonal damage in a range of neurological disorders, including multiple sclerosis, Alzheimer disease, frontotemporal dementia, amyotrophic lateral sclerosis, stroke and cerebrovascular disease, traumatic brain injury, and Parkinson disease. We also consider the steps needed to complete the translation of neurofilaments from the laboratory to the management of neurological diseases in clinical practice., (© 2024. Springer Nature Limited.)

Background and Objectives: The association between statin use and the risk of intracranial hemorrhage (ICrH) following ischemic stroke (IS) or transient ischemic attack (TIA) in patients with cerebral microbleeds (CMBs) remains uncertain. This study investigated the risk of recurrent IS and ICrH in patients receiving statins based on the presence of CMBs., Methods: We conducted a pooled analysis of individual patient data from the Microbleeds International Collaborative Network, comprising 32 hospital-based prospective studies fulfilling the following criteria: adult patients with IS or TIA, availability of appropriate baseline MRI for CMB quantification and distribution, registration of statin use after the index stroke, and collection of stroke event data during a follow-up period of ≥3 months. The primary endpoint was the occurrence of recurrent symptomatic stroke (IS or ICrH), while secondary endpoints included IS alone or ICrH alone. We calculated incidence rates and performed Cox regression analyses adjusting for age, sex, hypertension, atrial fibrillation, previous stroke, and use of antiplatelet or anticoagulant drugs to explore the association between statin use and stroke events during follow-up in patients with CMBs., Results: In total, 16,373 patients were included (mean age 70.5 ± 12.8 years; 42.5% female). Among them, 10,812 received statins at discharge, and 4,668 had 1 or more CMBs. The median follow-up duration was 1.34 years (interquartile range: 0.32-2.44). In patients with CMBs, statin users were compared with nonusers. Compared with nonusers, statin therapy was associated with a reduced risk of any stroke (incidence rate [IR] 53 vs 79 per 1,000 patient-years, adjusted hazard ratio [aHR] 0.68 [95% CI 0.56-0.84]), a reduced risk of IS (IR 39 vs 65 per 1,000 patient-years, aHR 0.65 [95% CI 0.51-0.82]), and no association with the risk of ICrH (IR 11 vs 16 per 1,000 patient-years, aHR 0.73 [95% CI 0.46-1.15]). The results in aHR remained consistent when considering anatomical distribution and high burden (≥5) of CMBs., Discussion: These observational data suggest that secondary stroke prevention with statins in patients with IS or TIA and CMBs is associated with a lower risk of any stroke or IS without an increased risk of ICrH., Classification of Evidence: This study provides Class III evidence that for patients with IS or TIA and CMBs, statins lower the risk of any stroke or IS without increasing the risk of ICrH.

Background: The transmission of amyloid β (Aβ) in humans leading to iatrogenic cerebral amyloid angiopathy (iCAA) is a novel concept with analogies to prion diseases. However, the number of published cases is low, and larger international studies are missing., Aims: We aimed to build a large multinational collaboration on iCAA to better understand the clinical spectrum of affected patients., Methods: We collected clinical data on patients with iCAA from Austria, Croatia, Italy, Slovenia, and Spain. Patients were included if they met the proposed Queen Square diagnostic criteria (QSC) for iCAA. In addition, we pooled data on disease onset, latency, and cerebrospinal fluid (CSF) biomarkers from previously published iCAA cases based on a systematic literature review., Results: Twenty-seven patients (22% women) were included in this study. Of these, 19 (70%) met the criteria for probable and 8 (30%) for possible iCAA. Prior neurosurgical procedures were performed in all patients (93% brain surgery, 7% spinal surgery) at median age of 8 (interquartile range (IQR) = 4-18, range = 0-26 years) years. The median symptom latency was 39 years (IQR = 34-41, range = 28-49). The median age at symptom onset was 49 years (IQR = 43-55, range = 32-70). Twenty-one patients (78%) presented with intracranial hemorrhage and 3 (11%) with seizures., Conclusions: Our large international case series of patients with iCAA confirms a wide age boundary for the diagnosis of iCAA. Dissemination of awareness of this rare condition will help to identify more affected patients., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Cerebral white matter hyperintensities (WMH) have been associated with subclinical atherosclerosis including coronary artery calcification (CAC). However, previous studies on this association are limited by only cross-sectional analysis. We aimed to explore the relationship between WMH and CAC in elderly individuals both cross-sectionally and longitudinally. The study population consisted of elderly stroke- and dementia-free participants from the community-based Austrian Stroke Prevention Family Study (ASPFS). WMH volume and CAC levels (via Agatston score) were analyzed at baseline and after a 6-year follow-up period. Of 324 study participants (median age: 68 years), 115 underwent follow-up. Baseline WMH volume (median: 4.1 cm 3 ) positively correlated with baseline CAC levels in multivariable analysis correcting for common vascular risk factors (p = 0.010). While baseline CAC levels were not predictive for WMH progression (p = 0.447), baseline WMH volume was associated CAC progression (median Agatston score progression: 27) in multivariable analysis (ß = 66.3 ± 22.3 [per cm 3 ], p = 0.004). Ten of 11 participants (91%) with severe WMH (Fazekas Scale: 3) at baseline showed significant CAC progression > 100 during follow-up. In this community-based cohort of elderly individuals, WMH were associated with CAC and predictive of its progression over a 6-year follow-up. Screening for coronary artery disease might be considered in people with more severe WMH., (© 2024. The Author(s).)

Introduction: Brain viscoelasticity as assessed by magnetic resonance elastography (MRE) has been discussed as a promising surrogate of microstructural alterations due to neurodegenerative processes. Existing studies indicate that multiple sclerosis (MS) is associated with a global reduction in brain stiffness. However, no study to date systematically investigated the MS-related characteristics of brain viscoelasticity separately in normal-appearing white matter (NAWM), deep gray matter (DGM) and T2-hyperintense white matter (WM) lesions., Methods: 70 MS patients and 42 healthy volunteers underwent whole-cerebral MRE using a stimulated echo sequence (DENSE) with a low-frequency mechanical excitation at 20 Hertz. The magnitude |G ∗ | (Pa) and phase angle φ (rad) of the complex shear modulus G ∗ were reconstructed by multifrequency dual elasto-visco (MDEV) inversion and related to structural imaging and clinical parameters., Results: We observed φ in the thalamus to be higher by 4.3 % in patients relative to healthy controls (1.11 ± 0.07 vs. 1.06 ± 0.07, p < 0.0001). Higher Expanded Disability Status Scale (EDSS) scores were negatively associated with φ in the basal ganglia (p = 0.01). We measured φ to be lower in MS lesions compared to surrounding NAWM (p = 0.001), which was most prominent for lesions in the temporal lobe (1.01 ± 0.22 vs. 1.06 ± 0.19, p = 0.003). Age was associated with lower values of |G ∗ | (p = 0.04) and φ (p = 0.004) in the thalamus of patients. No alteration in NAWM stiffness relative to WM in healthy controls was observed., Conclusion: Low-frequency elastography in MS patients reveals age-independent alterations in the viscoelasticity of deep gray matter at early stages of disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Endovascular therapy (EVT) has been established as a major component in the acute treatment of large vessel occlusion stroke. However, it is unclear whether outcome and other treatment-related factors differ if patients are treated within or outside core working hours., Methods: We analyzed data from the prospective nationwide Austrian Stroke Unit Registry capturing all consecutive stroke patients treated with EVT between 2016 and 2020. Patients were trichotomized according to the time of groin puncture into treatment within regular working hours (08:00-13:59), afternoon/evening (14:00-21:59) and night-time (22:00-07:59). Additionally, we analyzed 12 EVT treatment windows with equal patient numbers. Main outcome variables included favorable outcome (modified Rankin Scale scores of 0-2) 3 months post-stroke as well as procedural time metrics, recanalization status and complications., Results: We analyzed 2916 patients (median age 74 years, 50.7% female) who underwent EVT. Patients treated within core working hours more frequently had a favorable outcome (42.6% vs 36.1% treated in the afternoon/evening vs 35.8% treated at night-time; p=0.007). Similar results were found when analyzing 12 treatment windows. All these differences remained significant in multivariable analysis adjusting for outcome-relevant co-factors. Onset-to-recanalization time was considerably longer outside core working hours, which was mainly explained by longer door-to-groin time (p<0.001). There was no difference in the number of passes, recanalization status, groin-to-recanalization time and EVT-related complications., Conclusions: The findings of delayed intrahospital EVT workflows and worse functional outcomes outside core working hours in this nationwide registry are relevant for optimization of stroke care, and might be applicable to other countries with similar settings., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Poststroke epilepsy (PSE) represents an important complication of stroke. Data regarding the frequency and predictors of PSE in patients with large-vessel occlusion stroke receiving mechanical thrombectomy (MT) are scarce. Furthermore, information on acute and preexisting lesion characteristics on brain MRI has not yet been systematically considered in risk prediction of PSE. This study thus aims to assess PSE risk after acute ischemic stroke treated with MT, based on clinical and MRI features., Methods: In this multicenter study from two tertiary stroke centers, we included consecutive acute ischemic stroke patients who had received MT for acute intracranial large vessel occlusion (LVO) between 2011 and 2017, in whom post-interventional brain MRI and long term-follow-up data were available. Infarct size, affected cerebrovascular territory, hemorrhagic complications and chronic cerebrovascular disease features were assessed on MRI (blinded to clinical information). The primary outcome was the occurrence of PSE (> 7 days after stroke onset) assessed by systematic follow-up via phone interview or electronic records., Results: Our final study cohort comprised 348 thrombectomy patients (median age: 67 years, 45% women) with a median long-term follow-up of 78 months (range 0-125). 32 patients (9%) developed PSE after a median of 477 days (range 9-2577 days). In univariable analyses, larger postinterventional infarct size, infarct location in the parietal, frontal or temporal lobes and cerebral microbleeds were associated with PSE. Multivariable Cox regression analysis confirmed larger infarct size (HR 3.49; 95% CI 1.67-7.30) and presence of cerebral microbleeds (HR 2.56; 95% CI 1.18-5.56) as independent predictors of PSE., Conclusion: In our study, patients with large vessel occlusion stroke receiving MT had a 9% prevalence of PSE over a median follow-up period of 6.5 years. Besides larger infarct size, presence of cerebral microbleeds on brain MRI predicted PSE occurrence., (© 2023. The Author(s).)

Background: Increased middle cerebral artery (MCA) blood flow velocities on transcranial duplex sonography (TCD) were recently reported in individual patients after successful mechanical thrombectomy (MT) and were related to intracranial hemorrhage and poor outcome. However, the retrospective study design of prior studies precluded elucidation of the underlying pathomechanisms, and the relationship between TCD and brain parenchymal perfusion still remains to be determined., Methods: We prospectively investigated consecutive patients with stroke successfully recanalized by MT with TCD and MRI including contrast-enhanced perfusion sequences within 48 hours post-intervention. Increased MCA flow on TCD was defined as >30% mean blood flow velocity in the treated MCA compared with the contralateral MCA. MRI blood flow maps served to assess hyperperfusion rated by neuroradiologists blinded to TCD., Results: A total of 226 patients recanalized by MT underwent post-interventional TCD and 92 patients additionally had perfusion MRI. 85 patients (38%) had increased post-interventional MCA flow on TCD. Of these, 10 patients (12%) had an underlying focal stenosis. Increased TCD blood flow in the recanalized MCA was associated with larger infarct size, vasogenic edema, intracranial hemorrhage and poor 90-day outcome (all p≤0.005). In the subgroup for which both TCD and perfusion MRI were available, 29 patients (31%) had increased ipsilateral MCA flow velocities on TCD. Of these, 25 patients also showed parenchymal hyperperfusion on MRI (sensitivity 85%; specificity 62%). Hyperperfusion severity on MRI correlated with MCA flow velocities on TCD (r s =0.379, p<0.001)., Conclusions: TCD is a reliable bedside tool to identify post-reperfusion hyperperfusion, correlates well with perfusion MRI, and indicates risk of reperfusion injury after MT., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Patent foramen ovale (PFO)-closure is recommended for stroke prevention in selected patients with suspected PFO-associated stroke. However, studies on cerebrovascular event recurrence after PFO-closure are limited by relatively short follow-up periods and information on the underlying aetiology of recurrent events is scarce., Patients and Methods: All consecutive patients with a cerebral ischaemic event and PFO-closure at the University Hospital Graz were prospectively identified from 2004 to 2021. Indication for PFO-closure was based on a neurological-cardiological PFO board decision. Patients underwent standardized clinical and echocardiographic follow-up 6 months after PFO-closure. Recurrent cerebrovascular events were assessed via electronical health records., Results: PFO-closure was performed in 515 patients (median age: 49 years; Amplatzer PFO occluder: 42%). Over a median follow-up of 11 years (range: 2-18 years, 5141 total patient-years), recurrent ischaemic cerebrovascular events were observed in 34 patients (ischaemic stroke: n  = 22, TIA: n  = 12) and associated with age, hyperlipidaemia and smoking in multivariable analysis ( p  < 0.05 each). Large artery atherosclerosis and small vessel disease were the most frequent aetiologies of recurrent stroke/TIA (27% and 24% respectively), and only two events were related to atrial fibrillation (AF). Recurrent ischaemic cerebrovascular event rates and incident AF were comparable in patients treated with different PFO occluders ( p  > 0.1)., Discussion and Conclusion: In this long-term follow-up-study of patients with a cerebral ischaemic event who had received PFO-closure with different devices, rates of recurrent stroke/TIA were low and largely related to large artery atherosclerosis and small vessel disease. Thorough vascular risk factor control seems crucial for secondary stroke prevention in patients treated for PFO-related stroke.

Background: Although the incidence of stroke in the young is rising, data on long-term outcomes in these patients are scarce. We thus aimed to investigate the long-term risk of recurrent vascular events and mortality in a multicenter study., Methods: We followed 396 consecutive patients aged 18-55 years with ischemic stroke (IS) or transient ischemic attack (TIA) enrolled in three European centers during the period 2007-2010. A detailed outpatient clinical follow-up assessment was performed between 2018 and 2020. When an in-person follow-up visit was not possible, outcome events were assessed using electronic records and registry data., Results: During a median follow-up of 11.8 (IQR 10.4-12.7) years, 89 (22.5%) patients experienced any recurrent vascular event, 62 (15.7%) had any cerebrovascular event, 34 (8.6%) had other vascular events, and 27 (6.8%) patients died. Cumulative 10-year incidence rate per 1000 person-years was 21.6 (95% CI 17.1-26.9) for any recurrent vascular event and 14.9 (95% CI 11.3-19.3) for any cerebrovascular event. The prevalence of cardiovascular risk factors increased over time, and 22 (13.5%) patients lacked any secondary preventive medication at the in-person follow-up. After adjustment for demographics and comorbidities, atrial fibrillation at baseline was found to be significantly associated with recurrent vascular events., Conclusions: This multicenter study shows a considerable risk of recurrent vascular events in young IS and TIA patients. Further studies should investigate whether detailed individual risk assessment, modern secondary preventive strategies, and better patient adherence may reduce recurrence risk., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background Objectives: It is unclear whether IV thrombolysis (IVT) outperforms early dual antiplatelet therapy (DAPT) in the acute setting of mild ischemic stroke. The aim of this study was to compare the early safety and efficacy of IVT with that of DAPT., Methods: Data of mild noncardioembolic stroke patients with admission NIH Stroke Scale (NIHSS) score ≤3 who received IVT or early DAPT in the period 2018-2021 were extracted from a nationwide, prospective stroke unit registry. Study endpoints included symptomatic intracerebral hemorrhage (sICH), early neurologic deterioration ≥4 NIHSS points (END), and 3-month functional outcome by modified Rankin scale (mRS)., Results: A total of 1,195 mild stroke patients treated with IVT and 2,625 patients treated with DAPT were included. IVT patients were younger (68.1 vs 70.8 years), had less hypertension (72.8% vs 83.5%), diabetes (19% vs 28.8%), and a history of myocardial infarction (7.6% vs 9.2%), and slightly higher admission NIHSS scores (median 2 vs median 1) when compared with DAPT patients. After propensity score matching and multivariable adjustment, IVT was associated with sICH (4 [1.2%] vs 0) and END (adjusted odds ratio [aOR] 2.8, 95% CI 1.1-7.5), and there was no difference in mRS 0-1 at 3 months (aOR 1.3, 95% CI 0.7-2.6)., Discussion: This analysis from a prospective nationwide stroke unit network indicates that IVT is not superior to DAPT in the setting of mild noncardioembolic stroke and may eventually be associated with harm. Further research focusing on acute therapy of mild stroke is highly warranted., Classification of Evidence: This study provides Class III evidence that IVT is not superior to DAPT in patients with acute mild (NIHSS score ≤3) noncardioembolic stroke. The study lacks the statistical precision to exclude clinically important superiority of either therapy., (© 2023 American Academy of Neurology.)

Background and Objectives: Assessing the risk of recurrent intracerebral hemorrhage (ICH) is of high clinical importance. MRI-based cerebral small vessel disease (SVD) markers may help establish ICH etiologic subtypes (including cryptogenic ICH) relevant for recurrence risk., Methods: We investigated the risk of recurrent ICH in a large cohort of consecutive ICH survivors with available MRI at baseline. Patients with macrovascular, structural, or other identified secondary causes (other than SVD) were excluded. Based on MRI findings, ICH etiology was defined as probable cerebral amyloid angiopathy (CAA) according to the Boston 2.0 criteria, arteriolosclerosis (nonlobar ICH and additional markers of arteriolosclerosis, absent lobar hemorrhagic lesions), mixed SVD (mixed deep and lobar hemorrhagic changes), or cryptogenic ICH (no MRI markers of SVD). Recurrent ICH was determined using electronic health records and confirmed by neuroimaging. Data from an independent multicenter cohort (CROMIS-2 ICH) were used to confirm core findings., Results: Of 443 patients with ICH (mean age 67 ± 13 years, 41% female), ICH etiology was mixed SVD in 36.7%, arteriolosclerosis in 23.6%, CAA in 23.0%, and cryptogenic ICH in 16.7%. During a median follow-up period of 5.7 years (interquartile range 2.9-10.0, 2,682 patient-years), recurrent ICH was found in 59 individual patients (13.3%). The highest recurrence rate per 100 person-years was detected in patients with CAA (8.5, 95% CI 6.1-11.7), followed by that in those with mixed SVD (1.8, 95% CI 1.1-2.9) and arteriolosclerosis (0.6, 95% CI 0.3-1.5). No recurrent ICH occurred in patients with cryptogenic ICH during 510 person-years follow-up (97.5% CI 0-0.7); this finding was confirmed in an independent cohort (CROMIS-2 ICH, n = 216), in which also there was no recurrence in patients with cryptogenic ICH. In patients with CAA, cortical superficial siderosis was the imaging feature strongest related to ICH recurrence (hazard ratio 5.7, 95% CI 2.4-13.6)., Discussion: MRI-based etiologic subtypes are helpful in determining the recurrence risk of ICH; while the highest recurrence risk was found in CAA, recurrence risk was low for arteriolosclerosis and negligible for cryptogenic ICH., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Introduction: In malignant cerebral infarction decompressive hemicraniectomy has demonstrated beneficial effects, but the optimum size of hemicraniectomy is still a matter of debate. Some surgeons prefer a large-sized hemicraniectomy with a diameter of more than 14 cm (HC > 14). We investigated whether this approach is associated with reduced mortality and an improved long-term functional outcome compared to a standard hemicraniectomy with a diameter of less than 14 cm (HC ≤ 14)., Methods: Patients from the DESTINY (DEcompressive Surgery for the Treatment of malignant INfarction of the middle cerebral arterY) registry who received hemicraniectomy were dichotomized according to the hemicraniectomy diameter (HC ≤ 14 cm vs. HC > 14 cm). The primary outcome was modified Rankin scale (mRS) score ≤ 4 after 12 months. Secondary outcomes were in-hospital mortality, mRS ≤ 3 and mortality after 12 months, and the rate of hemicraniectomy-related complications. The diameter of the hemicraniectomy was examined as an independent predictor of functional outcome in multivariable analyses., Results: Among 130 patients (32.3% female, mean (SD) age 55 (11) years), the mean hemicraniectomy diameter was 13.6 cm. 42 patients (32.3%) had HC > 14. There were no significant differences in the primary outcome and mortality by size of hemicraniectomy. Rate of complications did not differ (HC ≤ 14 27.6% vs. HC > 14 36.6%, p = 0.302). Age and infarct volume but not hemicraniectomy diameter were associated with outcome in multivariable analyses., Conclusion: In this post-hoc analysis, large hemicraniectomy was not associated with an improved outcome or lower mortality in unselected patients with malignant middle cerebral artery infarction. Randomized trials should further examine whether individual patients could benefit from a large-sized hemicraniectomy., Clinical Trial Registration Information: German Clinical Trials Register (URL: https://www.drks.de ; Unique Identifier: DRKS00000624)., (© 2023. The Author(s).)

Competing Interests: Declaration of interests We declare no competing interests.

Competing Interests: Disclosures Dr Gattringer reports grants from Austrian Neurological Society, Austrian Science Fund, Amgen, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim and Novartis outside the submitted work. The other authors report no conflicts.

Background: Intracerebral hemorrhage (ICH) caused by cerebral amyloid angiopathy (CAA) has a high recurrence risk. The Boston criteria, while not designed to predict recurrence, are commonly used for in vivo diagnosis of CAA and have recently been revised to the version 2.0 (v2.0), introducing nonhemorrhagic white matter features. We investigated whether the new v2.0 criteria change ICH recurrence risk in patients with probable CAA., Methods: We assessed ICH recurrence risk in consecutive patients with ICH and available brain magnetic resonance imaging. Patients with macrovascular or structural causes were excluded. Recurrent ICH was determined using electronic health records and confirmed by neuroimaging. We compared ICH recurrence risk for Boston criteria v2.0 versus v1.5 for probable CAA using survival analysis., Results: Fifty-nine of 443 patients (13.3%) had recurrent ICH over a median follow-up of 5.7 years (2682 patient-years). Thirty-seven out of one hundred two patients (36.3%) with probable CAA according to the Boston criteria v2.0 had recurrent ICH compared with 36/82 patients (43.9%) according to the v1.5 criteria. Patients with probable CAA according to the Boston v1.5 criteria had a higher ICH recurrence rate (10.9 per 100 person-years [95% CI, 7.8-15.1]) compared with those diagnosed by the v2.0 criteria (8.5 per 100 person-years [95% CI, 6.1-11.7]). The 20 patients defined as probable CAA only by the v2.0 criteria had a very low recurrence rate (0.9 per 100 person-years [95% CI, 0.1-6.7]), lower than those diagnosed using the v1.5 criteria ( P <0.001)., Conclusions: Our findings suggest a wide spectrum of ICH recurrence risk in patients with probable CAA. Patients with ICH diagnosed with CAA based only on the nonhemorrhagic white matter markers introduced in the Boston v2.0 criteria had a much lower risk of recurrence than those diagnosed with the previous Boston criteria v1.5, comparable to that of patients with ICH not fulfilling any probable CAA criteria., Competing Interests: Disclosures Dr Gattringer reports travel grants from Bayer, Boehringer Ingelheim and Novartis, outside the submitted work. Dr Werring reports personal fees from Alexion, Alnylam, Bayer, Novo Nordisk, and Portola, outside the submitted work. The other authors report no potential conflicts of interest.

Background: Although decompressive hemicraniectomy (DHC) is a lifesaving treatment strategy for patients with malignant middle cerebral artery infarction (mMCAi), only one in four patients achieves low to moderate post-stroke disability according to previous studies. However, the short follow-up periods in prior studies could have overestimated the poor clinical prognosis. This study therefore examined the long-term outcome after DHC for mMCAi., Methods: We retrospectively included all patients who had undergone DHC after mMCAi at the University Hospital Graz between 2006 and 2019. Demographics, clinical data and complications were collected from electronic clinical patient records. To investigate long-term prognosis, all patients were followed up to 14 years after stroke including quality of life (QOL) assessment. Post-stroke disability was rated according to the modified Rankin Scale (mRS)., Results: Of 47 patients that had undergone DHC for mMCAi, follow-up data were available in 40 patients (mean age: 48 years; 40% female). Six months after the mMCAi, 14 patients had died (35%) and nine (23%) had a low to moderate post-stroke disability (mRS 0-3). Of 26 stroke survivors, half (50%) showed further mRS improvement (≥ 1 point) during the long-term follow-up period (mean follow-up time: 8 years). At last follow-up, 17 patients had achieved an mRS score of ≤ 3 (65% versus 35% after 6 months; p = 0.008) and 55% had no signs of depression and anxiety, and 50% no signs of pain or discomfort in QOL assessment., Conclusion: This study shows substantial long-term improvement of functional disability and reasonable QOL in mMCAi patients after DHC., (© 2023. The Author(s).)

Objectives: Cerebral microbleeds are associated with the risks of ischemic stroke and intracranial hemorrhage, causing clinical dilemmas for antithrombotic treatment decisions. We aimed to evaluate the risks of intracranial hemorrhage and ischemic stroke associated with microbleeds in patients with atrial fibrillation treated with vitamin K antagonists, direct oral anticoagulants, antiplatelets, and combination therapy (i.e. concurrent oral anticoagulant and antiplatelet)., Methods: We included patients with documented atrial fibrillation from the pooled individual patient data analysis by the Microbleeds International Collaborative Network. Risks of subsequent intracranial hemorrhage and ischemic stroke were compared between patients with and without microbleeds, stratified by antithrombotic use., Results: A total of 7,839 patients were included. The presence of microbleeds was associated with an increased relative risk of intracranial hemorrhage (adjusted hazard ratio [aHR] = 2.74, 95% confidence interval = 1.76-4.26) and ischemic stroke (aHR = 1.29, 95% confidence interval = 1.04-1.59). For the entire cohort, the absolute incidence of ischemic stroke was higher than intracranial hemorrhage regardless of microbleed burden. However, for the subgroup of patients taking combination of anticoagulant and antiplatelet therapy, the absolute risk of intracranial hemorrhage exceeded that of ischemic stroke in those with 2 to 4 microbleeds (25 vs 12 per 1,000 patient-years) and ≥ 11 microbleeds (94 vs 48 per 1,000 patient-years)., Interpretation: Patients with atrial fibrillation and high burden of microbleeds receiving combination therapy have a tendency of higher rate of intracranial hemorrhage than ischemic stroke, with potential for net harm. Further studies are needed to help optimize stroke preventive strategies in this high-risk group. ANN NEUROL 2023;94:61-74., (© 2023 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: Recently, arterial stiffness has been associated with cerebral small vessel disease (SVD), brain atrophy and vascular dementia. Arterial stiffness is assessed via pulse wave velocity (PWV) measurement and is strongly dependent on arterial blood pressure. While circadian blood pressure fluctuations are important determinants of end-organ damage, the role of 24-h PWV variability is yet unclear., Objectives: We here investigated the association between PWV and its circadian changes on brain morphology and cognitive function in community-dwelling individuals., Design: Single-centre, prospective, community-based follow-up study., Methods: The study cohort comprised elderly community-based participants of the Austrian Stroke Prevention Family Study which was started in 2006. Patients with any history of cerebrovascular disease or dementia were excluded. The study consists of 84 participants who underwent ambulatory 24-h PWV measurement. White matter hyperintensity volume and brain volume were evaluated by 3-Tesla magnetic resonance imaging (MRI). A subgroup of patients was evaluated for cognitive function using an extensive neuropsychological test battery., Results: PWV was significantly related to reduced total brain volume ( p  = 0.013), which was independent of blood pressure and blood pressure variability. We found no association between PWV with markers of cerebral SVD or impaired cognitive functioning. Only night-time PWV values were associated with global brain atrophy ( p  = 0.005)., Conclusions: This study shows a relationship of arterial stiffness and reduced total brain volume. Elevations in PWV during night-time are of greater importance than day-time measures., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2023.)

Background: Several blood biomarkers have been identified as predictors for poor outcome after ischemic stroke. However, recent studies mainly focused on single or experimental biomarkers and considered rather short follow-up intervals limiting their value for daily clinical practice. We, therefore, aimed to compare various clinical routine blood biomarkers for their predictive value on post-stroke mortality over a 5-year follow-up period., Patients and Methods: This data analysis of a prospective single-center study included all consecutive ischemic stroke patients admitted to the stroke unit of our university hospital over a 1-year period. Various blood biomarkers of inflammation, heart failure, metabolic disorders, and coagulation were analyzed from standardized routine blood samples collected within 24 h of hospital admission. All patients underwent a thorough diagnostic workup and were followed for 5 years post-stroke., Results: Of 405 patients (mean age: 70.3 years), 72 deceased (17.8%) during the follow-up period. While various routine blood biomarkers were associated with post-stroke mortality in univariable analyses, only NT-proBNP remained an independent predictor (adjusted odds ratio 5.1; 95% CI 2.0-13.1; p  < 0.001) for death after stroke. NT-proBNP levels ⩾794 pg/mL ( n  = 169, 42%) had a sensitivity of 90% for post-stroke mortality with a negative predictive value of 97% and was additionally associated with cardioembolic stroke and heart failure (each p  ⩽ 0.05)., Conclusion: NT-proBNP represents the most relevant routine blood-based biomarker for the prediction of long-term mortality after ischemic stroke. Increased NT-proBNP levels indicate a vulnerable subgroup of stroke patients in which early and thorough cardiovascular assessment and consistent follow-ups could improve outcome after stroke.

Background and Objectives: In patients with ischemic stroke (IS) or transient ischemic attack (TIA) and cortical superficial siderosis (cSS), there are few data regarding the risk of future cerebrovascular events and also about the benefits and safety of antithrombotic drugs for secondary prevention. We investigated the associations of cSS and stroke risk in patients with recent IS or TIA., Methods: We retrospectively analyzed the Microbleeds International Collaborative Network (MICON) database. We selected patients with IS or TIA from cohorts who had MRI-assessed cSS, available data on antithrombotic treatments, recurrent cerebrovascular events (intracranial hemorrhage [ICrH], IS, or any stroke [ICrH or IS]), and mortality. We calculated incidence rates (IRs) and performed univariable and multivariable Cox regression analyses., Results: Of 12,669 patients (mean age 70.4 ± 12.3 years, 57.3% men), cSS was detected in 273 (2.2%) patients. During a mean follow-up of 24 ± 17 months, IS was more frequent than ICrH in both cSS (IR 57.1 vs 14.6 per 1,000 patient-years) and non-cSS (33.7 vs 6.3 per 1,000 patient-years) groups. Compared with the non-cSS group, cSS was associated with any stroke on multivariable analysis {IR 83 vs 42 per 1,000 patient-years, adjusted hazard ratio [HR] for cSS 1.62 (95% CI: 1.14-2.28; p = 0.006)}. This association was not significant in subgroups of patients treated with antiplatelet drugs (n = 6,554) or with anticoagulants (n = 4,044). Patients with cSS who were treated with both antiplatelet drugs and anticoagulants (n = 1,569) had a higher incidence of ICrH (IR 107.5 vs 4.9 per 1,000 patient-years, adjusted HR 13.26; 95% CI: 2.90-60.63; p = 0.001) and of any stroke (IR 198.8 vs 34.7 per 1,000 patient-years, adjusted HR 5.03; 95% CI: 2.03-12.44; p < 0.001) compared with the non-cSS group., Discussion: Patients with IS or TIA with cSS are at increased risk of stroke (ICrH or IS) during follow-up; the risk of IS exceeds that of ICrH for patients receiving antiplatelet or anticoagulant treatment alone, but the risk of ICrH exceeds that of IS in patients receiving both treatments. The findings suggest that either antiplatelet or anticoagulant treatment alone should not be avoided in patients with cSS, but combined antithrombotic therapy might be hazardous. Our findings need to be confirmed by randomized clinical trials., (© 2022 American Academy of Neurology.)

Background: Serum glial fibrillary acidic protein (sGFAP) has been proposed as a biomarker in various neurological diseases but has not yet been systematically investigated in patients with cerebral small vessel disease (CSVD). We explored whether sGFAP levels are increased in stroke patients with MRI-confirmed recent small subcortical infarcts (RSSI) and analyzed the subsequent course and determinants of sGFAP longitudinally., Methods: In a prospectively-collected cohort of stroke patients with a single RSSI (n = 101, mean age: 61 years, 73% men), we analyzed brain MRI and sGFAP using a SIMOA assay at baseline and at 3- and 15-months post-stroke. Community-dwelling age- and sex-matched individuals (n = 51) served as controls., Results: RSSI patients had higher baseline sGFAP levels compared to controls (median: 187.4 vs. 118.3 pg/ml, p < 0.001), with no influence of the time from stroke symptom onset to baseline blood sampling (median 5 days, range 1-13). At the 3- and 15-months follow-up, sGFAP returned to control levels. While baseline sGFAP correlated with larger infarct size (r s  = 0.28, p = 0.01), neither baseline nor follow-up sGFAP levels were associated with chronic CSVD-related lesions (white matter hyperintensities, lacunes, microbleeds) after adjusting for age, sex and hypertension. Furthermore, sGFAP levels did not relate to the occurrence of new vascular brain lesions on follow-up MRI., Conclusions: sGFAP is increased in patients with CSVD-related stroke and correlates with the size of the RSSI. However, sGFAP levels were not related to chronic neuroimaging features or progression of CSVD, suggesting that sGFAP is sensitive to acute but not chronic cerebrovascular tissue changes in this condition., (© 2022. The Author(s).)

The incidence of thrombosis increases with aging. We investigated the coagulatory/haemostatic system across the ages and tested the hypothesis that older persons have a hypercoagulable state compared to younger persons at rest, and that standing up (orthostasis) leads to greater changes in coagulation in older persons. In total, 22 older and 20 young participants performed a 6 min sit-to-stand test (orthostatic challenge). Blood was collected prior to and at the end of standing and haemostatic profiling was performed via thrombelastometry (TEM), calibrated automated thrombogram (CAT) and standard coagulation assays. At baseline, three CAT-derived values indicated enhanced capability to generate thrombin in older participants. However, other measured parameters did not suggest a hypercoagulable state in older participants: prolonged TEM-derived coagulation times (295 vs. 209 s, medians, p = 0.0025) and prothrombin times (103 vs. 114%, medians, p = 0.0087), as well as lower TF levels (440 vs. 672 pg/mL, medians, p = 0.0245) and higher t-PA levels (7.3 vs. 3.8 ng/mL, medians, p = 0.0002), indicative of enhanced fibrinolytic capability, were seen. Younger participants were more sensitive to the orthostatic challenge: CAT-derived endogenous thrombin potentials (ETPs) were only increased in the young (1337 to 1350 nM.min, medians, p = 0.0264) and shortening of PTs was significantly higher in the young vs. older participants ( p = 0.0242). Our data suggest that the increased thrombosis propensity in older persons is not primarily attributable to a hyperactive coagulation cascade but may be due to other pathologies associated with aging.

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.

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., (© 2022 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background and Purpose: Studies on mechanical thrombectomy (MT) in acute ischemic stroke (AIS) patients with preexisting disability are limited. We aimed to compare the outcomes of MT versus best medical treatment (BMT) in these patients., Methods: In the nationwide Austrian registry and Swiss monocentric registry, we identified 462 AIS patients with pre-stroke disability (modified Rankin Scale [mRS] score ≥3) and acute large vessel occlusion. The primary outcome was returning to pre-stroke mRS or better at 3 months. Secondary outcomes were early neurological improvement (National Institutes of Health Stroke Scale score improvement ≥8 at 24 to 48 hours), 3-month mortality, and symptomatic intracerebral hemorrhage (sICH). Multivariable regression models and propensity score matching (PSM) were used for statistical analyses., Results: Compared with the BMT group (n=175), the MT group (n=175) had younger age, more severe strokes, and lower pre-stroke mRS, but similar proportion of receiving intravenous thrombolysis. MT was associated with higher odds of returning to baseline mRS or better at 3 months (adjusted odds ratio [aOR], 2.5; 95% confidence interval [CI], 1.39 to 4.47), early neurological improvement (aOR, 2.62; 95% CI, 1.41 to 4.88), and lower risk of 3-month mortality (aOR, 0.29; 95% CI, 0.18 to 0.49). PSM analysis showed similar findings. MT was not associated with an increased risk of sICH (4.0% vs. 2.1% in all patients; 4.2% vs. 2.4% in the PSM cohort)., Conclusions: MT in patients with pre-stroke mRS ≥3 might improve the 3-month outcomes and short-term neurological impairment, suggesting that pre-stroke disability alone should not be a reason to withhold MT, but that individual case-by-case decisions may be more appropriate.

Background and Purpose: With aging population, there is an increase of atrial fibrillation (AF) and other vascular risk factors. We investigated trends in stroke severity at hospital admission with respect to AF and other risk factors in a prospective national stroke registry from 2005 to 2020., Methods: Data from the prospective Austrian Stroke Unit Registry were used to study demographic and clinical factors associated with the change in admission stroke severity over years. Time trends in admission stroke severity of patients with pre-stroke modified Rankin Score ≤ 3 were investigated with respect to clinical variables and predefined age groups 18-54, 55-64, 65-74, 75-84 and ≥ 85 years. Time trends were studied using robust generalized linear models assuming normal distribution with a log link. Stroke severity on admission was assessed according to the National Institutes of Health Stroke Scale Score (NIHSS)., Results: In total, 140,312 patients with acute ischemic stroke were included in the analysis. Within the study period, mean patients' age increased from 70 to 72 years (p < 0.001) and median NIHSS at admission decreased from 4 to 3 (p < 0.001). The frequency of AF increased from 25 to 32% (p < 0.001). The decrease in median admission NIHSS was evident in all relevant subgroups but more pronounced in patients with risk factors including AF, diabetes, hypercholesterolemia, smoking, elderly patients and those with pre-stroke disability., Conclusion: Despite an aging population and generally increasing AF frequency, we observed a consistent trend towards less disabling strokes on admission., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Non-alcoholic fatty liver disease and particularly liver fibrosis are related to cardiovascular disease and may indicate an increased risk for atrial fibrillation (AF), but this association has not yet been systematically investigated in a cohort of ischemic stroke patients., Methods: We analyzed data from a prospective single-center study enrolling all consecutive ischemic stroke patients admitted to our stroke unit over a 1-year period. All patients received a thorough etiological workup. For evaluation of liver fibrosis, we determined the Fibrosis-4 (FIB-4) index, a well-established noninvasive liver fibrosis test. Laboratory results were analyzed from a uniform blood sample taken at stroke unit admission., Results: Of 414 included patients (mean age 70.2 years, 57.7% male), FIB-4 indicated advanced liver fibrosis in 92 (22.2%). AF as the underlying stroke mechanism was present in 28.0% (large vessel disease: 25.6%, small vessel disease: 11.4%, cryptogenic: 29.2%). Patients with FIB-4 ≥ 2.67 had higher rates of AF (53.3% vs. 20.8%, p &lt; 0.001), and this association remained significant after correction for established AF risk factors (odds ratio 2.53, 95% confidence interval 1.44-4.46, p = 0.001). FIB-4 was further associated with worse functional outcome 3 months (p &lt; 0.001) and higher mortality 4 years post-stroke (p &lt; 0.02), but these relationships were no longer present after correction for age and initial stroke severity. Moreover, FIB-4 was not associated with long-term recurrent vascular events., Conclusions: Liver fibrosis assessed by the FIB-4 index is independently associated with AF in acute ischemic stroke patients. Further studies should evaluate whether adding the FIB-4 index to AF risk scores increases their precision., (© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background and Purpose: Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year., Methods: We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020)., Results: There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observed. During the first 5 months of 2021, there was an increase in CVT volumes compared to 2019 (27.5%; 95% confidence interval [CI], 24.2 to 32.0; P<0.0001) and 2020 (41.4%; 95% CI, 37.0 to 46.0; P<0.0001). A COVID-19 diagnosis was present in 7.6% (132/1,738) of CVT hospitalizations. CVT was present in 0.04% (103/292,080) of COVID-19 hospitalizations. During the first pandemic year, CVT mortality was higher in patients who were COVID positive compared to COVID negative patients (8/53 [15.0%] vs. 41/910 [4.5%], P=0.004). There was an increase in CVT mortality during the first 5 months of pandemic years 2020 and 2021 compared to the first 5 months of the pre-pandemic year 2019 (2019 vs. 2020: 2.26% vs. 4.74%, P=0.05; 2019 vs. 2021: 2.26% vs. 4.99%, P=0.03). In the first 5 months of 2021, there were 26 cases of vaccine-induced immune thrombotic thrombocytopenia (VITT), resulting in six deaths., Conclusions: During the 1st year of the COVID-19 pandemic, CVT hospitalization volume and CVT in-hospital mortality did not change compared to the prior year. COVID-19 diagnosis was associated with higher CVT in-hospital mortality. During the first 5 months of 2021, there was an increase in CVT hospitalization volume and increase in CVT-related mortality, partially attributable to VITT.

Background: Patient-reported quality of life (QoL) may help to capture sequela of stroke more comprehensively. We aimed to investigate QoL in working age persons with ischemic stroke regarding impaired domains and identify factors associated with better QoL., Methods: We invited persons with stroke aged 18-55 years to participate in this prospective observational study. We assessed QoL and self-rated health using the EuroQol 5 Dimension questionnaire (EQ-5D) during hospital stay (baseline) and at 3-months follow-up (FU). Additionally, the National Institute of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), cognition (Montreal Cognitive assessment, MOCA), emotion (Hospital Anxiety and Depression Scale), and return to work were evaluated. We used hierarchical regression to identify predictors of QoL (self-rated health and QoL Index score) at FU., Results: We included 138 persons with stroke (mean age = 43.6 ± 10 years; 41% female; median admission NIHSS = 2), of whom 99 participated at FU. QoL Index and self-rated health were correlated with NIHSS, mRS, anxiety, and depression at both timepoints. Although 80% had favorable functional outcome at FU (mRS < 2), high proportions of these persons reported problems in the "Pain and/or Discomfort" (25.3%) and "Anxiety/Depression" (22.8%) dimensions. Only discharge NIHSS and baseline MOCA independently predicted self-rated health at FU. Female sex, higher discharge NIHSS, and higher baseline depression scores predicted worse QoL Index scores at FU., Conclusions: Three months post-stroke, working age persons with stroke frequently reported problems in dimensions not assessed by the routinely used mRS. Despite correlations between clinical scales and QoL, patient-reported outcomes and screening for cognition and emotion ensure a more comprehensive assessment of post-stroke consequences relevant for QoL., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pinter, Fandler-Höfler, Fruhwirth, Berger, Bachmaier, Horner, Eppinger, Kneihsl, Enzinger and Gattringer.)

Background: Cerebral venous thrombosis (CVT) is a multifactorial disease with a variety of related conditions and risk factors. Thyroid dysfunction-especially hyperthyroidism-has been linked to CVT, but this is mainly based on case reports ranging back to 1913, while systematic investigations addressing this issue are lacking. Therefore, we investigated the frequency and clinical characteristics of thyroid dysfunction in a large single-center cohort of CVT patients., Methods: We retrospectively identified all consecutive patients with aseptic CVT treated at our center between 2006 and 2020. Clinical information was extracted from our electronic medical documentation system. Thyroid-stimulating hormone (TSH) had been routinely measured at admission, free thyroid hormones and thyroid autoantibodies were analyzed whenever available., Results: Of 120 patients with imaging-confirmed CVT, our main analysis included 107 patients (mean age 42 ± 16 years, 74% female) in whom TSH measurements were available. Nineteen patients (17.8%, 95% confidence interval 10-25%) had thyroid dysfunction. Two had newly diagnosed hyperthyroidism (1.9%, 95% confidence interval 0-4%) caused by Graves' disease, but without typical symptoms for this condition. Seventeen patients (15.9%, 95% confidence interval 9-23%) had hypothyroidism (12 previously diagnosed with ongoing thyroid hormone replacement therapy; 5 with newly diagnosed subclinical hypothyroidism). Clinical CVT characteristics were similar comparing patients with versus without thyroid dysfunction., Conclusion: We observed a remarkably high prevalence of thyroid dysfunction in CVT patients. Whether this finding reflects a causal relationship warrants further studies. Despite that, the frequent coexistence of both diseases argues for TSH screening in CVT patients., (© 2021. The Author(s).)