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Objectives: Previous research demonstrated that the numerical Cincinnati Prehospital Stroke Scale (CPSS) identifies large vessel occlusion (LVO) at similar rates compared to dedicated LVO screening tools. We aimed to compare numerical CPSS to additional stroke scales using a national Emergency Medical Services (EMS) database., Methods: Using the ESO Data Collaborative, the largest EMS database with linked hospital data, we retrospectively analyzed prehospital patient records from 2022. Each EMS record was linked to corresponding emergency department (ED) and inpatient records through a data exchange platform. Prehospital CPSS was compared to the Cincinnati Stroke Triage Assessment Tool (C-STAT), the Field Assessment Stroke Triage for Emergency Destination (FAST-ED), and the Balance Eyes Face Arm Speech Time (BE-FAST). The optimal prediction cut points for LVO screening were determined by intersecting the sensitivity and specificity curves for each scale. To compare the discriminative abilities of each scale among those diagnosed with LVO, we used the area under the receiver operating curve (AUROC)., Results: We identified 17,442 prehospital records from 754 EMS agencies with ≥ 1 documented stroke scale of interest: 30.3% (n = 5,278) had a hospital diagnosis of stroke, of which 71.6% (n = 3,781) were ischemic; of those, 21.6% (n = 817) were diagnosed with LVO. CPSS score ≥ 2 was found to be predictive of LVO with 76.9% sensitivity, 68.0% specificity, and AUROC 0.787 (95% CI 0.722-0.801). All other tools had similar predictive abilities, with sensitivity/specificity/AUROC of: C-STAT 62.5%/76.5%/0.727 (0.555-0.899); FAST-ED 61.4%/76.1%/0.780 (0.725-0.836); BE-FAST 70.4%/67.1%/0.739 (0.697-0.788)., Conclusions: The less complex CPSS exhibited comparable performance to three frequently employed LVO detection tools. The EMS leadership, medical directors, and stroke system directors should weigh the complexity of stroke severity instruments and the challenges of ensuring consistent and accurate use when choosing which tool to implement. The straightforward and widely adopted CPSS may improve compliance while maintaining accuracy in LVO detection.

Background and Purpose: Coma is an independent predictor of poor clinical outcomes in cerebral venous thrombosis (CVT). We aimed to describe the association of age, sex, and radiological characteristics of adult coma patients with CVT., Methods: We used data from the international, multicentre prospective observational BEAST (Biorepository to Establish the Aetiology of Sinovenous Thrombosis) study. Only positively associated variables with coma with <10% missing data in univariate analysis were considered for the multivariate logistic regression model., Results: Of the 596 adult patients with CVT (75.7% women), 53 (8.9%) patients suffered coma. Despite being a female-predominant disease, the prevalence of coma was higher among men than women (13.1% vs. 7.5%, p = 0.04). Transverse sinus thrombosis was least likely to be associated with coma (23.9% vs. 73.3%, p < 0.001). The prevalence of superior sagittal sinus thrombosis was higher among men than women in the coma sample (73.6% vs. 37.5%, p = 0.01). Men were significantly older than women, with a median (interquartile range) age of 51 (38.5-60) versus 40 (33-47) years in the coma (p = 0.04) and 44.5 (34-58) versus 37 (29-48) years in the non-coma sample (p < 0.001), respectively. Furthermore, an age- and superior sagittal sinus-adjusted multivariate logistic regression model found male sex (odds ratio = 1.8, 95% confidence interval [CI] = 1.0-3.4, p = 0.04) to be an independent predictor of coma in CVT, with an area under the receiver operating characteristic curve of 0.61 (95% CI = 0.52-0.68, p = 0.01)., Conclusions: Although CVT is a female-predominant disease, men were older and nearly twice as likely to suffer from coma than women., (© 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background and Objectives: Gene-gene interactions likely contribute to the etiology of multifactorial diseases such as cerebral venous thrombosis (CVT) and could be one of the main sources of known missing heritability. We explored Factor XI ( F11 ) and ABO gene interactions among patients with CVT., Methods: Patients with CVT of European ancestry from the large Bio-Repository to Establish the Aetiology of Sinovenous Thrombosis (BEAST) international collaboration were recruited. Codominant modelling was used to determine interactions between genome-wide identified F11 and ABO genes with CVT status., Results: We studied 882 patients with CVT and 1,205 ethnically matched control participants (age: 42 ± 15 vs 43 ± 12 years, p = 0.08: sex: 71% male vs 68% female, p = 0.09, respectively). Individuals heterozygous (AT) for the risk allele (T) at both loci (rs56810541/ F11 and rs8176645/ ABO ) had a 3.9 (95% CI 2.74-5.71, p = 2.75e-13) increase in risk of CVT. Individuals homozygous (TT) for the risk allele at both loci had a 13.9 (95% CI 7.64-26.17, p = 2.0e-15) increase in risk of CVT. The presence of a non-O blood group (A, B, AB) combined with TT/rs56810541/ F11 increased CVT risk by OR = 6.8 (95% CI 4.54-10.33, p = 2.00e15), compared with blood group-O combined with AA., Discussion: Interactions between factor XI and ABO genes increase risk of CVT by 4- to 14-fold.

Background: The association between vascular risk factors and cervical artery dissections (CeADs), a leading cause of ischemic stroke (IS) in the young, remains controversial., Objectives: This study aimed to explore the causal relation of vascular risk factors with CeAD risk and recurrence and compare it to their relation with non-CeAD IS., Methods: This study used 2-sample Mendelian randomization analyses to explore the association of blood pressure (BP), lipid levels, type 2 diabetes, waist-to-hip ratio, smoking, and body mass index with CeAD and non-CeAD IS. To simulate effects of the most frequently used BP-lowering drugs, this study constructed genetic proxies and tested their association with CeAD and non-CeAD IS. In analyses among patients with CeAD, the investigators studied the association between weighted genetic risk scores of vascular risk factors and the risk of multiple or early recurrent dissections., Results: Genetically determined higher systolic BP (OR: 1.51; 95% CI: 1.32-1.72) and diastolic BP (OR: 2.40; 95% CI: 1.92-3.00) increased the risk of CeAD (P < 0.0001). Genetically determined higher body mass index was inconsistently associated with a lower risk of CeAD. Genetic proxies for β-blocker effects were associated with a lower risk of CeAD (OR: 0.65; 95% CI: 0.50-0.85), whereas calcium-channel blockers were associated with a lower risk of non-CeAD IS (OR: 0.75; 95% CI: 0.63-0.90). Weighted genetic risk scores for systolic BP and diastolic BP were associated with an increased risk of multiple or early recurrent CeAD., Conclusions: These results are supportive of a causal association between higher BP and increased CeAD risk and recurrence and provide genetic evidence for lower CeAD risk under β-blockers. This may inform secondary prevention strategies and trial design for CeAD., Competing Interests: Funding Support and Author Disclosures The CADISP (Cervical Artery Dissection and Ischemic stroke Patients) study has been supported by Institut National de la Santé et de la Recherche Médicale, Lille 2 University, Institut Pasteur de Lille and Lille University Hospital; and has received funding from the ERDF (European Research and Development Funds) and Région Nord-Pas-de-Calais in the frame of Contrat de Projets Etat-Region 2007-2013 Région Nord-Pas-de-Calais (grant 09120030), Centre National de Genotypage, Emil Aaltonen Foundation, Paavo Ilmari Ahvenainen Foundation, Helsinki University Central Hospital Research Fund, Helsinki University Medical Foundation, Päivikki and Sakari Sohlberg Foundation, Aarne Koskelo Foundation, Maire Taponen Foundation, Aarne and Aili Turunen Foundation, Lilly Foundation, Alfred Kordelin Foundation, Finnish Medical Foundation, Orion Farmos Research Foundation, Maud Kuistila Foundation, the Finnish Brain Foundation, Biomedicum Helsinki Foundation, Projet Hospitalier de Recherche Clinique Régional, Fondation de France, Génopôle de Lille, Adrinord, Basel Stroke-Funds, Käthe-Zingg-Schwichtenberg-Fonds of the Swiss Academy of Medical Sciences, and Swiss Heart Foundation. Computations were supported by the Bordeaux Bioinformatics Center (CBiB) and the CREDIM (Centre de Recherche et Développement en Informatique Médicale), with the generous support of the Fondation Claude Pompidou (to S.D.). Dr Le Grand has received funding from the Digital Public Health Graduate Program, a PhD program supported by the French Investment for the Future Programme (17-EURE-0019). Dr Southerland has received payment for expert legal consultation in the United States for cases pertaining to CeAD and stroke. Prof Markus has received research support from the National Institute for Health and Care Research Cambridge Biomedical Research Centre (BRC-1215-20014) and the Cambridge British Heart Foundation Centre of Research Excellence (RE/18/1/34212). Prof Thijs has received speaker and/or consulting fees from Boehringer Ingelheim, Bayer, Pfizer, Bristol Myers Squibb, Medtronic, Abbott, and Allergan. Prof Leys is Editor-in-Chief of European Journal of Neurology. Prof Debette has received grant support overseen by the French National Research Agency as part of the “Investment for the Future Programme” (ANR-18-RHUS-0002) by the European Union’s Horizon 2020 Research and Innovation Programme (grants 640643 and 754517). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Lacunar infarcts and vascular dementia are important phenotypic characteristics of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, the most common inherited cerebral small vessel disease. Individuals with the disease show variability in the nature and onset of symptoms and rates of progression, which are only partially explained by differences in pathogenic mutations in the NOTCH3 gene. Recognizing the disease early in its course and securing a molecular diagnosis are important clinical goals, despite the lack of proven disease-modifying treatments. The purposes of this scientific statement are to review the clinical, genetic, and imaging aspects of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, contrasting it with other inherited small vessel diseases, and to provide key prevention, management, and therapeutic considerations with the intent of reducing practice variability and encouraging production of high-quality evidence to support future treatment recommendations.

Objective: To examine preliminary effects of ReStoreD (Resilience after Stroke in Dyads) on resilience in couples coping with stroke-related challenges., Design: Supplemental analysis of prospective pilot trial with pre-/post-assessments and 3-month follow-up., Setting: Community., Participants: Thirty-four cohabitating stroke-care partner dyads (N=34); at least 3 months post-stroke., Interventions: 8-week self-administered dyadic intervention (ReStoreD) consisting of activities completed individually and as a couple., Main Outcome Measures: 10-item Connor-Davidson Resilience Scale., Results: Care partner baseline resilience scores were significantly higher than persons with stroke scores. Repeated-measures analysis of variance suggest significant pre-post improvement in resilience for persons with stroke (mean difference [I - J]=-2.42, SE=.91, P=.04, 95% CI [-4.75, -0.08]) with a large effect size (η 2 =.34), which was maintained at 3-month follow-up. Care partners showed no significant change over time., Conclusions: This study provides preliminary evidence that ReStoreD improves resilience in persons with stroke. More research is needed to address resilience in care partners. These findings represent a promising first step to address the mental health needs in this population., (Copyright © 2023 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: In 2017, the Centers for Disease Control and Prevention (CDC) issued an alert that, after decades of consistent decline, the stroke death rate levelled off in 2013, particularly in younger individuals and without clear origin. The objective of this analysis was to understand whether social determinants of health have influenced trends in stroke mortality., Methods: We performed a longitudinal analysis of county-level ischemic and hemorrhagic stroke death rate per 100,000 adults from 1999 to 2018 using a Bayesian spatiotemporally smoothed CDC dataset stratified by age (35-64 years [younger] and 65 years or older [older]) and then by county-level social determinants of health. We reported stroke death rate by county and the percentage change in stroke death rate during 2014-2018 compared with that during 2009-2013., Results: We included data from 3,082 counties for younger individuals and 3,019 counties for older individuals. The stroke death rate began to increase for younger individuals in 2013 ( p < 0.001), and the slope of the decrease in stroke death rate tapered for older individuals ( p < 0.001). During the 20-year period of our study, counties with a high social deprivation index and ≥10% Black residents consistently had the highest rates of stroke death in both age groups. Comparing stroke death rate during 2014-2018 with that during 2009-2013, larger increases in younger individuals' stroke death rate were seen in counties with ≥90% (vs <90%) non-Hispanic White individuals (3.2% mean death rate change vs 1.7%, p < 0.001), rural (vs urban) populations (2.6% vs 2.0%, p = 0.019), low (vs high) proportion of medical insurance coverage (2.9% vs 1.9%, p = 0.002), and high (vs low) substance abuse and suicide mortality (2.8 vs 1.9%, p = 0.008; 3.3% vs 1.5%, p < 0.001). In contrast to the younger individuals, in older individuals, the associations with increased death rates were with more traditional social determinants of health such as the social deprivation index, urban location, unemployment rate, and proportion of Black race and Hispanic ethnicity residents., Discussion: Improvements in the stroke death rate in the United States are slowing and even reversing in younger individuals and many US counties. County-level increases in stroke death rate were associated with distinct social determinants of health for younger vs older individuals. These findings may inform targeted public health strategies., (© 2023 American Academy of Neurology.)

Introduction: Telestroke (TS) networks are standard in many areas of the US. Despite TS systems having approximately 33% mimic rates, it is unknown if TS can accurately diagnose patients with acute ischemic stroke (AIS) versus stroke mimics., Methods: We performed a retrospective review of consecutive TS consults to 27 TS sites in six states during 2018. Clinical information and diagnosis were extracted from discharge records and compared to those from the TS consult. Discharge diagnoses were verified and coded into 12 categories. Cases without a clear discharge diagnosis and intracerebral haemorrhage were excluded. We report agreement and a Cohen's kappa between TS and discharge diagnoses for the category of AIS/transient ischemic attack (TIA) versus stroke mimic., Results: We included 404 cases in the analysis (mean age 66 years; 54% women). Of these, 225 had a TS diagnosis of AIS/TIA; 102 (45%) received intravenous tissue plasminogen activator. Our study demonstrated a high diagnostic agreement for AIS/TIA (88%) with a kappa of 0.75 for stroke and mimics. Of the 179 patients diagnosed with a stroke mimic on TS, 27 (15%) were diagnosed with AIS/TA by discharge. TS mimic diagnosis had a positive predictive value (PPV) of 85% and a negative predictive value (NPV) of 90%; TS diagnosis of stroke/TIA had PPV 90%, NPV 85%., Discussion: We found excellent correlation between TS and discharge diagnoses for patients with both stroke and stroke mimics. This suggests that TS systems can accurately assess a wider variety of patients with acute neurologic syndromes other than AIS.

Background: Migraine is associated with neuroimaging differences in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). However, it is unknown if migraine-related disability (MRD) or if calcitonin gene-related peptide (CGRP), a vasoactive peptide important in migraine pathology, have radiographic implications. The aims of this study were to identify whether MRD or interictal serum CGRP levels impacted neuroimaging findings for those with CADASIL., Materials and Methods: A cross-sectional analysis was performed. The primary outcomes were neuroimaging differences associated with MRD among those with migraine or interictal serum CGRP levels of those with and without migraine. MRD was defined by 2 migraine disability scales (Migraine Disability Assessment, Headache Impact Test-6). Retrospective brain magnetic resonance imaging was reviewed (average 1.7 ± 2.0 y before enrollment). Rank-sum and χ 2 tests were used., Results: Those with migraine (n=25, vs. n=14 without) were younger [median 49 (25 to 82) y vs. 60 (31 to 82) y, P <0.007], had fewer cerebral microbleeds (0 to 31 vs. 0 to 50, P =0.02) and less frequently had anterior temporal lobe T2 hyperintensities [68% (17/25) vs 100% (14/14), P =0.02]. MRD scale outcomes had no significant radiographic associations. Interictal serum CGRP did not differ (migraine: n=18, 27.0±9.6 pg/mL vs. no migraine: n=10, 26.8±15.7 pg/mL, P =0.965)., Conclusions: Migraine may forestall microangiopathy in CADASIL, though possibly independent of severity as measured by MRD. Interictal serum CGRP did not differ in our cohort suggesting CGRP may not be vital to migraine pathophysiology in CADASIL. Larger studies are needed to account for age differences., Competing Interests: E.D.G. received support from the NH-NINDS U24NS107228; compensation from Medlink. A.d.H. who reports support by the NIH-NINDS K23NS105924; consultation for Integra; investigator-initiated support from Regeneron, Amgen, and AMAG pharmaceuticals. PG, PLD, JFH, MPL, HB reports no disclosures. JJM receives support from the NH-NINDS U24NS107228; associate editor, Stroke. J.F.M. receives funding from the NINDS for work related to the CREST2 trial and the DISCOVERY trial. The remaining authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Women with hypertensive disorders of pregnancy (HDP) have an increased risk of cardiovascular disease. Whether HDP is also associated with later-life dementia has not been fully explored., Methods: Using the Utah Population Database, we performed an 80-year retrospective cohort study of 59,668 parous women., Results: Women with, versus without, HDP, had a 1.37 higher risk of all-cause dementia (95% confidence interval [CI]: 1.26, 1.50) after adjustment for maternal age at index birth, birth year, and parity. HDP was associated with a 1.64 higher risk of vascular dementia (95% CI: 1.19, 2.26) and 1.49 higher risk of other dementia (95% CI: 1.34, 1.65) but not Alzheimer's disease dementia (adjusted hazard ratio = 1.04; 95% CI: 0.87, 1.24). Gestational hypertension and preeclampsia/eclampsia showed similar increased dementia risk. Nine mid-life cardiometabolic and mental health conditions explained 61% of HDP's effect on subsequent dementia risk., Discussion: Improved HDP and mid-life care could reduce the risk of dementia., Competing Interests: The authors declare no conflicts of interest. Author disclosures are available in the supporting information., (© 2023 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)

Background: Abbreviated "rapid MRI" protocols have become more common for the evaluation of acute ischemic stroke (AIS). Prior research has not evaluated the effect of rapid MRIs on cost or hospital length of stay in AIS patients., Methods: We retrospectively identified AIS patients who presented within 6 h of acute neurologic symptom onset to an emergency department (ED) and activated a "brain attack" code. We included sequential patients from January 2012 to September 2015, before rapid MRI was available, who had CT perfusion (CTP) and compared them to patients from October 2015 to May 2018 who had a rapid MRI. We used inverse-probability-weighting (IPW) to balance the cohorts. The primary outcomes were direct cost to our healthcare system and total hospital length of stay (LOS)., Results: We included 408 brain attack activations (mean ± SD age 62.1 ± 17.6 years, 47.8% male): 257 in the CTP cohort and 151 in the MRI cohort. Discharge diagnosis was ischemic stroke in 193/408 (47.3%). After patient matching, we found significant reductions for the MRI cohort in total cost (-18.7%, 95% CI -35.0, -2.4, p = 0.02) and hospital LOS (-17.0%, 95% CI -31.2, -2.8, p = 0.02), with no difference in ED LOS ( p = 0.74) as compared to the CTP cohort., Conclusion: Although these results are preliminary and hypothesis-generating, we found that the use of a rapid MRI protocol in emergency department brain attacks was associated with a 18.7% reduction in total direct cost and 17% reduction in hospital length of stay.

Objectives: Emergency Medicine (EM) provider experiences consulting telestroke (TS) are poorly studied. In this qualitative study, we aimed to determine how TS changes patient management and to measure TS effects on EM provider confidence with acute ischemic stroke (AIS) treatment., Materials and Methods: We designed a survey for EM providers querying perceptions of TS value, confidence with treating AIS, and counterfactuals regarding what EM providers would have done without TS. Eligible EM providers participated in an audio-visual TS consult within a 6-state TS network between 11/2016-11/2017., Results: We received 48 surveys (response rate 43%). The most common reason (71%) for using TS was tPA eligibility expert opinion. Most EM providers (94%) thought the patient/family were satisfied with TS and none felt their medical knowledge was doubted because of using TS. EM providers had high confidence in diagnosing AIS (95%) and tPA decision-making (86%), but not in determining thrombectomy eligibility (10%). Among EM providers who administered tPA, 85% said tPA would not have been given without TS consultation. TS consultation changed patient diagnosis in 60% of all patients and treatment plans in 56% of non-stroke patients. Most EM providers (86%) had increased confidence in their knowledge of future stroke patient management. Nearly all TS consults (93%) resulted in EM providers being more likely to use TS again., Conclusions: TS consult frequently results in both patient management change and increased EM knowledge of stroke management with increased likelihood of repeat usage. Discomfort in determining eligibility for thrombectomy points to educational opportunities., Competing Interests: 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., (© 2023 The Authors.)

Background: Cerebral venous thrombosis (CVT) is an uncommon cause of stroke in young adults. We aimed to determine the impact of age, gender and risk factors (including sex-specific) on CVT onset., Methods: We used data from the BEAST (Biorepository to Establish the Aetiology of Sinovenous Thrombosis), a multicentre multinational prospective observational study on CVT. Composite factors analysis (CFA) was performed to determine the impact on the age of CVT onset in males and females., Results: A total of 1309 CVT patients (75.3% females) aged ⩾18 years were recruited. The overall median (IQR-interquartile range) age for males and females was 46 (35-58) years and 37 (28-47) years ( p  < 0.001), respectively. However, the presence of antibiotic-requiring sepsis ( p  = 0.03, 95% CI 27-47 years) among males and gender-specific risk factors like pregnancy ( p  < 0.001, 95% CI 29-34 years), puerperium ( p  < 0.001, 95% CI 26-34 years) and oral contraceptive use ( p  < 0.001, 95% CI 33-36 years) were significantly associated with earlier onset of CVT among females. CFA demonstrated a significantly earlier onset of CVT in females, ~12 years younger, in those with multiple (⩾1) compared to '0' risk factors ( p  < 0.001, 95% CI 32-35 years)., Conclusions: Women suffer CVT 9 years earlier in comparison to men. Female patients with multiple (⩾1) risk factors suffer CVT ~12 years earlier compared to those with no identifiable risk factors., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© European Stroke Organisation 2023.)

Background: Higher blood pressure variability (BPV) is associated with the development of major vascular diseases, independent of mean blood pressure. However, despite data indicating that serum inflammatory markers are linked to hypertension, the association between serum inflammatory markers and BPV has not been studied in humans., Methods: This is a post hoc analysis of the Multi-Ethnic Study of Atherosclerosis (MESA) study. The study exposure was tertiles of serum level of interleukin-6 (IL-6), C-reactive protein (CRP), d-dimer, plasmin-antiplasmin complex (PAP), fibrinogen antigen, and calibrated Factor VIII (%) at the baseline study visit. The primary outcome was visit-to-visit BPV measured as the residual standard deviation (rSD) of at least 4 study visits (2000-2018). Two logistic regression models were fit to the top tertile of rSD during follow-up: in Model 1, we adjusted for age, sex, and hypertension, and in Model 2, for patient age categories, sex, race/ethnicity, education, hypertension, diabetes, smoking, drinking, body mass index, lipid-lowering medication, and mean systolic blood pressure., Results: Our analysis included 5,483 patients, with a mean (SD) age of 61.4 (10.0) years, 52.9% female, and 40.7% White. In unadjusted analyses, all markers of inflammation were associated with higher BPV, but after adjustment, only IL-6 retained significance (P < 0.001). The odds ratio for the highest tertile of BPV and IL-6 was 1.49 (95% confidence interval [CI] 1.28-1.74, P < 0.001)., Conclusions: Baseline serum IL-6 was associated with increased subsequent BPV in a large multiracial cohort. Further investigation is needed to better understand the relationship between chronic inflammation and BPV., (© The Author(s) 2022. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Patients with acute ischaemic strokes (AIS), on average, fare better with timely neurologist consultation, and a growing proportion of them receive one. However, little is known about trends in the characteristics of neurologists who treat AIS., Methods: We identified AIS and transient ischaemic attack (TIA) episodes with neurologist consults in fee-for-service Medicare from January 2008 to September 2021. For each episode, we determined whether the neurologist was a vascular neurologist, was a high-volume provider, whether the patient was transferred between hospitals and the distance between the patient's home and physician's practice., Results: From 2008 to 2021, the share of AIS/TIA episodes (n=5 073 294) with neurologist consults increased (52.9% to 61.7%). Among episodes with consults, the fraction conducted by a vascular neurologist (5.2% to 13.7%) or by a high-volume neurologist (13.2% to 14.9%) also increased. The fraction with the patient's home and neurologist greater than 100 miles apart (4.8% to 9.6%) or in different states (5.1% to 8.1%) increased, as did the fraction with transfers (4.2% to 8.5%)., Discussion: Over the study period, the proportion of AIS/TIA episodes with consultations from neurologists with either vascular neurology certifications or high volumes increased substantially., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Prior meta-analyses report a 2- to 4-fold increased risk of later cardiovascular disease among women with a history of hypertensive disorders of pregnancy (HDP). Given HDP's vascular underpinnings, it is hypothesized to also be a risk factor for later dementia. We aim to summarize the evidence for the impact of HDP on dementia and consider unique associations between HDP and dementia subtypes., Methods: Observational studies on the relationship between HDP and dementia were identified from online electronic databases to July 1, 2021 (PROSPERO identifier: CRD42020185630). We included observational studies published in English. Exposure among women was any HDP and HDP subtypes: gestational hypertension, preeclampsia/eclampsia, or other/unspecified HDP. Outcome was any dementia and dementia subtypes: Alzheimer's disease, vascular dementia, or other/unspecified dementias., Results: For our primary analyses, we included 5 cohort studies with a total of 183 874 women with and 2 309 705 women without HDP. Pooled analysis found a 38% higher risk of all-cause dementia among women with, versus without, any type of HDP (adjusted hazard ratio, 1.38 [95% CI, 1.18-1.61]; P <0.01). When examining association by HDP and dementia subtypes, we found that women with, versus without, any type of HDP had over a 3-fold higher risk of vascular dementia (adjusted hazard ratio, 3.14 [95% CI, 2.32-4.24]; P <0.01)., Conclusions: Our findings indicate that maternal history of HDP is an important risk factor for later development of vascular and all-cause dementia. Further research among more racially/ethnically diverse populations quantifying HDP's effect on all-cause dementia, and specifically vascular dementia, is warranted.

Purpose: Many individuals with stroke require informal caregiver support. These caregivers are often unprepared and overwhelmed. This study assesses the feasibility and acceptability of GETCare, a remote Goal-based Education and skills Training program for Caregivers caring for an individual poststroke., Design: Single-arm mixed-methods pilot trial was performed., Methods: The GETCare program is a 5-week remote, individually administered program for informal stroke caregivers that includes education, skills training, guided goal setting, and resource recommendations. Quantitative data were analyzed using descriptive statistics and qualitative data via a deductive approach., Results: Twenty-eight caregivers were recruited with 18 caregivers completing the program. These 18 caregivers reported high satisfaction, and over 75% reported program content was at least quite helpful. Caregivers suggested that the length of the program was appropriate, indicated that weekly check-ins were helpful, and supported this program for informal caregivers across the time trajectory poststroke. Eight of 10 caregivers who dropped out of the program were caring for someone 0-4 months poststroke., Conclusions: Caregivers positively received the GETCare program, which was uniquely structured to provide resources and skills for this high-need population. This pilot study provides valuable insight for future remote interventions poststroke., Clinical Relevance to Practice of Nursing: Results provide foundational knowledge in how to better support caregivers through guided goal setting and individualized education., (Copyright © 2022 Association of Rehabilitation Nurses.)

Ischemic stroke prompts a strong inflammatory response, which is associated with exacerbated outcomes. In this study, we investigated mechanistic regulators of neutrophil extracellular trap (NET) formation in stroke and whether they contribute to stroke outcomes. NET-forming neutrophils were found throughout brain tissue of ischemic stroke patients, and elevated plasma NET biomarkers correlated with worse stroke outcomes. Additionally, we observed increased plasma and platelet surface-expressed high-mobility group box 1 (HMGB1) in stroke patients. Mechanistically, platelets were identified as the critical source of HMGB1 that caused NETs in the acute phase of stroke. Depletion of platelets or platelet-specific knockout of HMGB1 significantly reduced plasma HMGB1 and NET levels after stroke, and greatly improved stroke outcomes. We subsequently investigated the therapeutic potential of neonatal NET-inhibitory factor (nNIF) in stroke. Mice treated with nNIF had smaller brain infarcts, improved long-term neurological and motor function, and enhanced survival after stroke. nNIF specifically blocked NET formation without affecting neutrophil recruitment after stroke. Importantly, nNIF also improved stroke outcomes in diabetic and aged mice and was still effective when given 1 hour after stroke onset. These results support a pathological role for NETs in ischemic stroke and warrant further investigation of nNIF for stroke therapy.

Ischemic stroke is a worldwide problem, with 15 million people experiencing a stroke annually. MR imaging is a valuable tool for understanding and assessing brain changes after stroke and predicting recovery. Of particular interest is the use of diffusion MR imaging in the nonacute stage 1-30 days poststroke. Thousands of articles have been published on the use of diffusion MR imaging in stroke, including several recent articles reviewing the use of DTI for stroke. The goal of this work was to survey and put into context the recent use of diffusion MR imaging methods beyond DTI, including diffusional kurtosis, generalized fractional anisotropy, spherical harmonics methods, and neurite orientation and dispersion models, in patients poststroke. Early studies report that these types of beyond-DTI methods outperform DTI metrics either in being more sensitive to poststroke changes or by better predicting outcome motor scores. More and larger studies are needed to confirm the improved prediction of stroke recovery with the beyond-DTI methods., (© 2022 by American Journal of Neuroradiology.)

Introduction: Continuous surveillance of stroke admissions has been conducted in the Hunter region, Australia, over the past two decades. We aimed to describe the trends in incidence rates of hospitalised stroke and case-fatality rates in this region, 2001-2019., Methods: From a hospital-based stroke registry, data for admitted adult stroke patients residing in the Hunter region were collected using ICD-10 codes for ischemic and haemorrhagic stroke. Negative binomial regression and logistic regression analysis were used to analyse trends for age-standardised and age-specific incidence rates of hospitalised stroke and 28-day case-fatality rates., Results: A total of 14,662 hospitalisations for stroke in 13,242 individuals were registered. The age-standardised incidence rate declined from 123 per 100,000 population in the 2001-2005 epoch to 96 in the 2016-2019 epoch (mean annual change -2.0%, incidence rate ratio (IRR) = 0.980 [95%CI: 0.976-0.984]). Age-specific analyses identified significant reduction in the group aged 75-84 (1039 per 100,000 population in 2001-2005 to 633 in 2016-2019, annual change -3.5%, IRR= 0.965 [95%CI: 0.960-0.970]). The 28-day case-fatality rates fluctuated over time (18.5% in 2001-2005, 20.8% in 2010-2015, and 17.8% in 2016-2019).  Projected population aging suggests annual volume of patients with new stroke will increase by 77% by 2041 if incidence rates remain unchanged at the 2016-2019 level., Conclusion: Although age-standardised hospitalised stroke incidence rates have declined in the Hunter region, the health system will face an increase in stroke hospitalisations related to the aging population., Competing Interests: Conflict of Interest The author(s) declared there is no potential conflicts of interest with publication of this article., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

In the Furthering Access to Stroke Telemedicine (FAST) Act, passed as part of a budget omnibus in 2018, Congress permanently expanded Medicare payment for telemedicine consultations for acute stroke ("telestroke") from delivery only in rural areas to delivery in both urban and rural areas, effective January 1, 2019. Using a controlled time-series analysis, we found that one year after FAST Act implementation, billing for Medicare telestroke increased substantially in emergency departments at both directly affected urban hospitals and indirectly affected rural hospitals. However, at that time only a minority of hospitals with known telestroke capacity had ever billed Medicare for that service, and there was substantial billing inconsistent with Medicare requirements. As Congress considers options for Medicare telemedicine payment after the COVID-19 pandemic, our findings, which are consistent with confusion among providers regarding telemedicine billing requirements, suggest that simplified payment rules would help ensure that expanded reimbursement achieves its intended impact.

Stroke affects not only the survivor but also their romantic partner. Post-stroke depression is common in both partners and can have significant negative consequences, yet few effective interventions are available. The purpose of this study was to pilot test a novel 8-week remotely administered dyadic intervention (ReStoreD) designed to help couples better cope with stroke-related changes and reduce depressive symptoms. Thirty-four cohabitating survivor-partner dyads at least 3 months post-stroke and reporting some changes in mood were enrolled. Depressive symptoms were assessed pre- and post-intervention and at 3-month follow-up. Repeated measures analysis of variance was used to assess the effects of ReStoreD over time on depressive symptoms in stroke survivors and their partners. Twenty-six dyads completed the study. Although statistical significance was not reached, there was a large effect size for improvements in depressive symptoms for stroke survivors. There was no significant improvement for partners, and the effect size was minimal. Those with more significant depressive symptoms at baseline were more likely to benefit from the intervention. This pilot study established proof-of-concept by demonstrating that depressive symptoms can be lessened in stroke survivors and partners with more severe depressive symptoms. Future research will establish the efficacy of the intervention in a fully powered study.

Background: Studies demonstrate an association between visit-to-visit blood pressure variability (BPV) and cardiovascular events and death. We aimed to determine the long-term cardiovascular and mortality effects of BPV in midlife in participants with and without cardiovascular risk factors., Methods: This is a post-hoc analysis of the Atherosclerosis Risk in the Community study. Long-term BPV was derived utilizing mean systolic blood pressure at Visits 1-4 (Visit 1: 1987-1989, Visit 2: 1990-1992, Visit 3: 1993-1995, Visit 4: 1996-1998). The primary outcome was mortality from Visit 4 to 2016 and secondary outcome was cardiovascular events (fatal coronary heart disease, myocardial infarction, cardiac procedure, or stroke). We fit Cox proportional hazards models and also performed the analysis in a subgroup of cardiovascular disease-free patients without prior stroke, myocardial infarction, congestive heart failure, hypertension, or diabetes., Results: We included 9,578 participants. The mean age at the beginning of follow-up was 62.9 ± 5.7 years, and mean follow-up was 14.2 ± 4.5 years. During follow-up, 3,712 (38.8%) participants died and 1,721 (n = 8,771, 19.6%) had cardiovascular events. For every SD higher in systolic residual SD (range 0-60.5 mm Hg, SD = 5.6 mm Hg), the hazard ratio for death was 1.09 (95% confidence interval [CI] 1.05-1.12) and for cardiovascular events was 1.00 (95% CI 0.95-1.05). In cardiovascular disease-free participants (n = 4,452), the corresponding hazard ratio for death was 1.12 (95% CI 1.03-1.21) and for cardiovascular events was 1.01 (95% CI 0.89-1.14)., Conclusion: Long-term BPV during midlife is an independent predictor of later life mortality but not cardiovascular events., (© American Journal of Hypertension, Ltd 2021. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background and Purpose: Brain cavernous angiomas with symptomatic hemorrhage (CASH) have a high risk of neurological disability from recurrent bleeding. Systematic assessment of baseline features and multisite validation of novel magnetic resonance imaging biomarkers are needed to optimize clinical trial design aimed at novel pharmacotherapies in CASH., Methods: This prospective, multicenter, observational cohort study included adults with unresected, adjudicated brain CASH within the prior year. Six US sites screened and enrolled patients starting August 2018. Baseline demographics, clinical and imaging features, functional status (modified Rankin Scale and National Institutes of Health Stroke Scale), and patient quality of life outcomes (Patient-Reported Outcomes Measurement Information System-29 and EuroQol-5D) were summarized using descriptive statistics. Patient-Reported Outcomes Measurement Information System-29 scores were standardized against a reference population (mean 50, SD 10), and one-sample t test was performed for each domain. A subgroup underwent harmonized magnetic resonance imaging assessment of lesional iron content with quantitative susceptibility mapping and vascular permeability with dynamic contrast-enhanced quantitative perfusion., Results: As of May 2020, 849 patients were screened and 110 CASH cases enrolled (13% prevalence of trial eligible cases). The average age at consent was 46±16 years, 53% were female, 41% were familial, and 43% were brainstem lesions. At enrollment, ≥90% of the cohort had independent functional outcome (modified Rankin Scale score ≤2 and National Institutes of Health Stroke Scale score <5). However, perceived health problems affecting quality of life were reported in >30% of patients (EuroQol-5D). Patients had significantly worse Patient-Reported Outcomes Measurement Information System-29 scores for anxiety ( P =0.007), but better depression ( P =0.002) and social satisfaction scores ( P =0.012) compared with the general reference population. Mean baseline quantitative susceptibility mapping and permeability of CASH lesion were 0.45±0.17 ppm and 0.39±0.31 mL/100 g per minute, respectively, which were similar to historical CASH cases and consistent across sites., Conclusions: These baseline features will aid investigators in patient stratification and determining the most appropriate outcome measures for clinical trials of emerging pharmacotherapies in CASH.

Objective: Cerebral venous thrombosis (CVT) is an uncommon form of stroke affecting mostly young individuals. Although genetic factors are thought to play a role in this cerebrovascular condition, its genetic etiology is not well understood., Methods: A genome-wide association study was performed to identify genetic variants influencing susceptibility to CVT. A 2-stage genome-wide study was undertaken in 882 Europeans diagnosed with CVT and 1,205 ethnicity-matched control subjects divided into discovery and independent replication datasets., Results: In the overall case-control cohort, we identified highly significant associations with 37 single nucleotide polymorphisms (SNPs) within the 9q34.2 region. The strongest association was with rs8176645 (combined p = 9.15 × 10 -24 ; odds ratio [OR] = 2.01, 95% confidence interval [CI] = 1.76-2.31). The discovery set findings were validated across an independent European cohort. Genetic risk score for this 9q34.2 region increases CVT risk by a pooled estimate OR = 2.65 (95% CI = 2.21-3.20, p = 2.00 × 10 -16 ). SNPs within this region were in strong linkage disequilibrium (LD) with coding regions of the ABO gene. The ABO blood group was determined using allele combination of SNPs rs8176746 and rs8176645. Blood groups A, B, or AB, were at 2.85 times (95% CI = 2.32-3.52, p = 2.00 × 10 -16 ) increased risk of CVT compared with individuals with blood group O., Interpretation: We present the first chromosomal region to robustly associate with a genetic susceptibility to CVT. This region more than doubles the likelihood of CVT, a risk greater than any previously identified thrombophilia genetic risk marker. That the identified variant is in strong LD with the coding region of the ABO gene with differences in blood group prevalence provides important new insights into the pathophysiology of CVT. ANN NEUROL 2021;90:777-788., (© 2021 American Neurological Association.)

Background and Purpose: Left atrial (LA) cardiac disease is a suspected cause of embolic stroke of undetermined source (ESUS). We tested the hypothesis that LA fibrosis, quantified using late-gadolinium-enhancement magnetic resonance imaging (LGE-MRI), predicts recurrent stroke or atrial fibrillation (AF) in patients with ESUS., Methods: We compared atrial fibrosis in healthy controls and patients with lacunar stroke, ESUS, and known AF with or without prior stroke. We followed patients with ESUS prospectively for the primary outcome of recurrent ischemic stroke, incident AF, or both., Results: We enrolled 203 patients from three centers: 103 patients without AF (35 healthy controls, 15 with lacunar strokes, 53 with ESUS) and 100 patients with AF (50 with and 50 without prior stroke). Patients with ESUS had significantly higher atrial fibrosis (15.0 ± 6.2%) compared to healthy controls (8.1 ± 7.9%; <0.0001) and compared to lacunar stroke patients (10.8 ± 8.4; p = 0.02), but had comparable fibrosis to patients with AF with (17.9 ± 11.4%) or without prior stroke (16.6 ± 9.2%; p = NS for both). Over a mean follow-up of 19 months, nine of 53 patients (16.9%) with ESUS experienced the combined primary outcome, which included six patients (11.3%) with recurrent ischemic stroke and five patients with incident AF (9.4%). Patients with ESUS with fibrosis ≥12% had a higher proportion of the combined outcome: 25.0% vs. 4.8%; p = 0.039., Conclusions: Patients with ESUS demonstrate atrial fibrosis comparable to that seen in AF. Atrial fibrosis ≥12% was associated with recurrent stroke, incident AF or both. This subgroup of ESUS patients may benefit from anticoagulation for secondary prevention of ischemic stroke., (© 2021 European Academy of Neurology.)

Introduction: We evaluated the association between carotid compliance, a measure of arterial stiffness, to parahippocampal volume (PHV) and hippocampal volume (HV) over 20 years later in the Atherosclerosis Risk in the Community study., Methods: We included participants with common carotid compliance measurements at visit 1 (1987-1989) and volumetric brain MRI at visit 5 (2011-2013). The primary outcomes are pooled bilateral PHV and HV. We performed linear regression models adjusting for age, sex, vascular risk factors, and total brain volume., Results: Of the 614 participants, higher compliance was correlated with higher PHV ( R = 0.218[0.144-0.291], p < 0.001) and HV ( R = 0.181 [0.105-0.255, p < 0.001]). The association was linear and significant after adjusting for confounders. At follow-up MRI, 30 patients with dementia had lower PHV and HV than patients without dementia ( p < 0.001 and p < 0.001, respectively)., Conclusion: Carotid compliance is associated with higher PHV and HV when measured 20 years later, further supporting the link between arterial stiffness and cognitive decline., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2021 by S. Karger AG, Basel.)

The aim of the present European Stroke Organisation guideline is to provide clinically useful evidence-based recommendations on the management of extracranial artery dissection (EAD) and intracranial artery dissection (IAD). EAD and IAD represent leading causes of stroke in the young, but are uncommon in the general population, thus making it challenging to conduct clinical trials and large observational studies. The guidelines were prepared following the Standard Operational Procedure for European Stroke Organisation guidelines and according to GRADE methodology. Our four recommendations result from a thorough analysis of the literature comprising two randomized controlled trials (RCTs) comparing anticoagulants to antiplatelets in the acute phase of ischemic stroke and twenty-six comparative observational studies. In EAD patients with acute ischemic stroke, we recommend using intravenous thrombolysis (IVT) with alteplase within 4.5 hours of onset if standard inclusion/exclusion criteria are met, and mechanical thrombectomy in patients with large vessel occlusion of the anterior circulation. We further recommend early endovascular or surgical intervention for IAD patients with subarachnoid hemorrhage (SAH). Based on evidence from two phase 2 RCTs that have shown no difference between the benefits and risks of anticoagulants versus antiplatelets in the acute phase of symptomatic EAD, we strongly recommend that clinicians can prescribe either option. In post-acute EAD patients with residual stenosis or dissecting aneurysms and in symptomatic IAD patients with an intracranial dissecting aneurysm and isolated headache, there is insufficient data to provide a recommendation on the benefits and risks of endovascular/surgical treatment. Finally, nine expert consensus statements, adopted by 8 to 11 of the 11 experts involved, propose guidance for clinicians when the quality of evidence was too low to provide recommendations. Some of these pertain to the management of IAD (use of IVT, endovascular treatment, and antiplatelets versus anticoagulation in IAD with ischemic stroke and use of endovascular or surgical interventions for IAD with headache only). Other expert consensus statements address the use of direct anticoagulants and dual antiplatelet therapy in EAD-related cerebral ischemia, endovascular treatment of the EAD/IAD lesion, and multidisciplinary assessment of the best therapeutic approaches in specific situations., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© European Stroke Organisation 2021.)