Numerical Cincinnati Stroke Scale versus Stroke Severity Screening Tools for the Prehospital Determination of LVO.

Background: Previous research demonstrated that the numerical Cincinnati Prehospital Stroke Scale (CPSS) identifies large vessel occlusion (LVO) at similar rates compared to a limited number of stroke severity screening tools. We aimed to compare numerical CPSS to additional stroke scales using a national EMS database. Methods: Using the ESO Data Collaborative, the largest EMS database with hospital linked data, we retrospectively analyzed prehospital patient records for the year 2022. Stroke and LVO diagnoses were determined by ICD-10 codes from linked hospital discharge and emergency department records. 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). Conclusion: The less complex CPSS exhibited comparable performance to three frequently employed LVO detection tools. EMS agency leadership, medical directors, stroke system directors, and other stroke leaders may consider the complexity of stroke severity instruments and challenges with ensuring accurate recall and consistent application when selecting which instrument to implement. Use of the simpler CPSS may enhance compliance with the utilization of LVO screening instruments while maintaining the accuracy of prehospital LVO determination.

Gene-Gene Interaction Between Factor-XI and ABO Genes in Cerebral Venous Thrombosis: The BEAST Study.

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.

Coma in adult cerebral venous thrombosis: The BEAST study.

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.

Genetic Insights on the Relation of Vascular Risk Factors and Cervical Artery Dissection.

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 ß-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 ß-blockers. This may inform secondary prevention strategies and trial design for CeAD.

Management of Inherited CNS Small Vessel Diseases: The CADASIL Example: A Scientific Statement From the American Heart Association.

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.

Hypertensive disorders of pregnancy and subsequent risk of Alzheimer's disease and other dementias.

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.

Age of onset of cerebral venous thrombosis: the BEAST study.

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.

Promoting Resilience After Stroke in Dyads (ReStoreD): A Supplemental Analysis.

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 (η2=.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.

CGRP, Migraine, and Brain MRI in CADASIL: A Pilot Study.

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.

Telestroke consultation can accurately diagnose ischemic stroke mimics.

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.

Direct cost analysis of rapid MRI in the emergency department evaluation of patients suspected of having acute ischemic stroke*.

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.

Trends in characteristics of neurologists who provide stroke consultations in the USA, 2008-2021.

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.

Baseline Serum Biomarkers of Inflammation and Subsequent Visit-to-Visit Blood Pressure Variability: A Post Hoc Analysis of MESA.

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.

Association Between Hypertensive Disorders of Pregnancy and Dementia: a Systematic Review and Meta-Analysis.

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.

Piloting GETCare: A Goal-Based Education and Skills Training Program for Caregivers.

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.