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There has been a plethora of studies focused on female-specific risk factors and sex differences in stroke published in the past year. This article summarizes several of those novel studies which provide new knowledge about the field of stroke in women. The Nurses’ Health Study II provides new data on the association between laparoscopically proven endometriosis and future stroke, accounting for the mediation effects of hysterectomy and oophorectomy. In a cohort of women from China, the relationship between hysterectomy, oophorectomy, and stroke is further clarified, accounting for the age at which the procedure is performed. The UK Biobank study provides new information on the relationship between oral contraceptive and hormone replacement therapy and stroke, with analytical techniques that focus on the timing of events related to duration of exposure. Finally, 2 new meta-analyses address the question of whether sex differences exist in the presentation of stroke symptoms.

Hemianopia (unilateral blindness), a common consequence of stroke and trauma to visual cortex, is a debilitating disorder for which there are few treatments. Research in an animal model has suggested that visual-auditory stimulation therapy, which exploits the multisensory architecture of the brain, may be effective in restoring visual sensitivity in hemianopia. It was tested in two male human patients who were hemianopic for at least 8 months following a stroke. The patients were repeatedly exposed to congruent visual-auditory stimuli within their blinded hemifield during 2 h sessions over several weeks. The results were dramatic. Both recovered the ability to detect and describe visual stimuli throughout their formerly blind field within a few weeks. They could also localize these stimuli, identify some of their features, and perceive multiple visual stimuli simultaneously in both fields. These results indicate that the multisensory therapy is a rapid and effective method for restoring visual function in hemianopia.SIGNIFICANCE STATEMENTHemianopia (blindness on one side of space) is widely considered to be a permanent disorder. Here, we show that a simple multisensory training paradigm can ameliorate this disorder in human patients.

Stroke patients discharged home often require prolonged assistance from caregivers. Little is known about the real-world effectiveness of a comprehensive stroke transitional care intervention on relieving caregiver strain. To describe the effect of the COMPASS transitional care (COMPASS-TC) intervention on caregiver strain and characterize the types, duration, and intensity of caregiving. The cluster-randomized COMPASS pragmatic trial evaluated the effectiveness of COMPASS-TC versus usual care with patients with mild stroke and TIA at 40 hospitals in North Carolina, USA. Of 5882 patients enrolled, 4208 (71%) identified a familial caregiver. A follow-up Caregiver Questionnaire, including the Modified Caregiver Strain Index, was administered at approximately three months post-discharge. Demographics and frequency, duration, and intensity of caregiving were compared between groups. 1228 caregivers (29%) completed the questionnaire. Completion was positively associated with older patient age, white race, and spousal relationship. One-third of the caregivers provided ≥30 hours of care per week and 889 (79%) provided care ≥9 weeks. Average standardized caregiver strain was 21.9 (0–100), increasing with stroke severity and comorbidity burden. Women caregivers reported higher strain than men. Treatment allocation was not associated with caregiver strain. This sample of mild stroke and TIA survivors received significant assistance from familial caregivers. However, caregiver strain was relatively low. Findings support the importance of familial caregiving in stroke, the continued disproportionate burden on women within the family, and the need for future research on caregiver support.

Introduction: Suboptimal sleep duration and poor sleep quality have been proposed to increase stroke risk. However, their significance in young ischemic stroke is unclear. We aimed to investigate the importance of sleep duration and quality on young ischemic stroke patients. Methods: A multicenter matched case-control study was performed to evaluate under-recognized risk factors in young (

Atrial fibrillation (AF) is one of the strongest risk factors for ischemic stroke, which is a leading cause of disability and death. Given the aging population, increasing prevalence of AF risk factors, and improved survival in those with cardiovascular disease, the number of individuals affected by AF will continue increasing over time. While multiple proven stroke prevention therapies exist, important questions remain about the optimal approach to stroke prevention at the population and individual patient levels. Our report summarizes the National Heart, Lung, and Blood Institute virtual workshop focused on identifying key research opportunities related to stroke prevention in AF. The workshop reviewed major knowledge gaps and identified targeted research opportunities to advance stroke prevention in AF in the following areas: (1) improving risk stratification tools for stroke and intracranial hemorrhage; (2) addressing challenges with oral anticoagulants; and (3) delineating the optimal roles of percutaneous left atrial appendage occlusion and surgical left atrial appendage closure/excision. This report aims to promote innovative, impactful research that will lead to more personalized, effective use of stroke prevention strategies in people with AF.

Background: While several studies have examined care transitions following stroke, few have assessed use of rehabilitation. We explored factors predictive of referral to community-based rehabilitation following stroke. Setting: 40 NC acute care hospitals that participated in the COMprehensive Post-Acute Stroke Services study from 2016-2019. Participants: Adults discharged home following stroke or TIA (N=11,195) Methods: Guided by an a priori conceptual framework, 41 predictors of referral to community-based rehabilitation were grouped into 3 patient-level domains: demographics, stroke severity, and medical history (e.g., prior stroke); 2 hospital-level domains: structural characteristics (e.g., bed size) and stroke-specific characteristics (e.g., stroke center status); and 1 community-level domain (county-level therapist supply). We estimated predictors of referral using a logistic mixed model with a hospital-specific random effect. We used a hierarchical backward selection approach, first performing domain-specific model selection, then entering retained variables into a complete model. Results: The cohort was 49% female, 72% white, with a mean age of 66.8 (SD=14.0) years and overall low stroke severity [mean [SD] NIHSS 2.4 [3.8]). Thirty-six percent of patients were referred to rehabilitation. Referral varied across hospitals, ranging from 3-78%, with a median of 35%. In the final model, older age, female sex, non-white race, higher stroke severity, longer length of stay, previous stroke, current smoking, and heart failure were associated with higher odds of referral as was hospital-employed vs. external-contracted OT services (Table). Discussion: Approximately one-third of stroke survivors discharged home were referred to community-based rehabilitation. Women and non-white patients had higher odds of referral. Hospital and community factors were largely not independent predictors of referral. Unmeasured process measures may play a role in unexplained hospital variation.

Background: Post-stroke depression (PSD) affects about one third of stroke survivors and is associated with poorer quality of life. Little is known about the prevalence and independent risk factors for depression associated with small vessel stroke (SVS). Methods: We conducted a retrospective analysis of a prospective cohort of patients enrolled in the American Stroke Association-Bugher SVS Study, which enrolled 200 patients within 2 years of SVS and 79 controls without stroke history from 2007 to 2012 at four clinical sites. The primary outcome was PHQ-8 dichotomized at (≥10 and Results: The cohort included 161 participants with SVS (excluding 39 due to missing key variables) and 79 controls. Participant characteristics are described in Table 1. The mean time between stroke and depression screening was 74 days. Among participants with SVS, 31.7% (n=51) screened positive for PSD, compared to 6.3% (n=5) of controls, OR= 6.9 (95%CI 2.6-18.0%; p Conclusion: In this well-characterized cohort of SVS with mostly mild stroke severity, depression within 3 months of the incident stroke was about 7 times more likely than those without a history of stroke. The extent of WMD was not associated with PSD, suggesting that small vessel disease other than the incident SVS does not account for the increased rates of PSD. Depression following SVS was more prevalent in women.

Migraine is reportedly associated with several cardio-cerebrovascular diseases (CCDs), but some of these diseases have not received sufficient attention. We thus attempted to determine the associations of migraine with peripheral arterial disease (PAD), ischemic heart disease (IHD), atrial fibrillation/flutter (AF), ischemic stroke (IS), and hemorrhagic stroke (HS).The study population was recruited by applying International Classification of Diseases, Tenth Revision (ICD-10) codes to the database of the Korean National Health Insurance Service from 2002 to 2018. Cumulative incidence curves were plotted to compare the incidence rates of CCDs between the migraine (ICD-10 code G43;For all CCDs, the cumulative incidence rates were higher in the migraine group than the nonmigraine group (Associations of migraine with CCDs have been demonstrated, which are stronger in females than in males.

Ischemic stroke during pregnancy is relatively rare, but when it occurs, the risk is highest in the postpartum period. This is a condition that requires immediate recognition and evaluation for acute management to potentially prevent devastating neurological consequences. Determining an etiology while considering physiological changes during and after pregnancy is also important. Post-stroke care including implementing secondary stroke prevention via pharmacological and non-pharmacological methods is regular practice. Consideration of physical, occupational, and speech therapy strategies as well as lifestyle modification and evaluation and treatment of co-morbid psychiatric conditions is also paramount. Postpartum care and consideration of future pregnancies and hormonal changes that may occur is also important.

Intracerebral hemorrhage (ICH) during pregnancy and the puerperuim is a rare but potentially devastating complication of pregnancy. It is a condition that requires emergent medical attention and inclusion of multiple medical and or surgical specialists. Accurate diagnosis based on clinical exam and supported by neuroimaging techniques is essential. Medical management is the mainstay in most cases including post-hemorrhage blood product consideration, reversal agents if on anti-coagulation, blood pressure control, cerebral edema management, and treatment of seizures. Circumstances also arise in which surgical intervention is needed. It is important to also discuss optimal timing of delivery. Postpartum care including close blood pressure control, deep vein thrombosis prophylaxis (DVT), and risk factor modification are important. Ethical situations sometimes arise and must also be considered with respect to the mother and child.

Background and Purpose— This guideline provides an overview of the evidence on established and emerging risk factors for stroke to provide evidence-based recommendations for the reduction of risk of a first stroke. Methods— Writing group members were nominated by the committee chair on the basis of their previous work in relevant topic areas and were approved by the American Heart Association (AHA) Stroke Council Scientific Statement Oversight Committee and the AHA Manuscript Oversight Committee. The writing group used systematic literature reviews (covering the time since the last review was published in 2006 up to April 2009), reference to previously published guidelines, personal files, and expert opinion to summarize existing evidence, indicate gaps in current knowledge, and when appropriate, formulate recommendations using standard AHA criteria ( Tables 1 and 2 ). All members of the writing group had the opportunity to comment on the recommendations and approved the final version of this document. The guideline underwent extensive peer review by the Stroke Council leadership and the AHA scientific statements oversight committees before consideration and approval by the AHA Science Advisory and Coordinating Committee. Results— Schemes for assessing a person's risk of a first stroke were evaluated. Risk factors or risk markers for a first stroke were classified according to potential for modification (nonmodifiable, modifiable, or potentially modifiable) and strength of evidence (well documented or less well documented). Nonmodifiable risk factors include age, sex, low birth weight, race/ethnicity, and genetic predisposition. Well-documented and modifiable risk factors include hypertension, exposure to cigarette smoke, diabetes, atrial fibrillation and certain other cardiac conditions, dyslipidemia, carotid artery stenosis, sickle cell disease, postmenopausal hormone therapy, poor diet, physical inactivity, and obesity and body fat distribution. Less well-documented or potentially modifiable risk factors include the metabolic syndrome, excessive alcohol consumption, drug abuse, use of oral contraceptives, sleep-disordered breathing, migraine, hyperhomocysteinemia, elevated lipoprotein(a), hypercoagulability, inflammation, and infection. Data on the use of aspirin for primary stroke prevention are reviewed. Conclusion— Extensive evidence identifies a variety of specific factors that increase the risk of a first stroke and that provide strategies for reducing that risk.

Introduction: Stroke patients are the second highest post-acute rehabilitation users but there are few comparisons of inpatient rehabilitation (IRF) and skilled nursing facility (SNF) care on patient-reported outcomes. Methods: We compared 3 and 12 month dependence (modified Rankin Scale score=3-6), quality of life (QOL) (Euro-qol-5D continuous variable max=1; death=0), and institutionalization (residence recorded as nursing home, hospice or dead) for acute ischemic stroke (AIS) patients in GWTG-Stroke and the AVAIL (Adherence eValuation After Ischemic Stroke Longitudinal) study living at home pre-stroke and discharged to an IRF or SNF immediately after hospital discharge. Binary and continuous outcomes were modeled by logistic and linear regression, respectively. Inverse propensity weighting (IPW) was used to adjust for measured differences in demographic, clinical and hospital characteristics. Results: Of 473 AIS patients, 72% were discharged to IRFs vs 27% to SNFs. IRF compared with SNF patients were 73 vs. 77 years, with 23% vs. 18% ambulating independently at hospital discharge. After IPW adjustment patients who received IRF care reported better QOL and were less likely to be institutionalized at 3- and 12-months than those who received SNF care but the difference in dependence was not statistically significant (Table). In sensitivity analyses among patients with a NIHSS score, QOL at 3-months was significantly better for IRF compared with SNF patients with no other differences between groups. Conclusions: AIS patients referred to IRFs had higher QOL at 3-months and lower odds of institutionalization at 3 and 12 months post stroke compared with patients referred to SNFs. Further research is needed to discern the mechanisms for potential differences in patient reported outcomes between settings.

Background —Hypercoagulable states are a recognized, albeit uncommon, etiology of ischemic stroke. It is unclear how often the results of specialized coagulation tests affect management. Using data compiled from a systematic review of available studies, we employed quantitative methodology to assess the diagnostic yield of coagulation tests for identification of coagulopathies in ischemic stroke patients. Summary of Review —We performed a MEDLINE search to identify controlled studies published during 1966–1999 that reported the prevalence of deficiencies of protein C, protein S, antithrombin III, plasminogen, activated protein C resistance (APCR)/factor V Leiden mutation (FVL), anticardiolipin antibodies (ACL), or lupus anticoagulant (LA) in patients with ischemic stroke. The cumulative prevalence rates (pretest probabilities) and positive likelihood ratios for all studies and for those including only patients aged ≤50 years were used to calculate posttest probabilities for each coagulopathy, reflecting diagnostic yield. The cumulative pretest probabilities of coagulation defects in ischemic stroke patients are as follows: LA, 3% (8% for those aged ≤50 years); ACL, 17% (21% for those aged ≤50 years); APCR/FVL, 7% (11% for those aged ≤50 years); and prothrombin mutation, 4.5% (5.7% for those aged ≤50 years). The posttest probabilities of ACL, LA, and APCR increased with increasing pretest probability, the specificity of the tests, and features of the patients’ history and clinical presentation. Conclusions —–The pretest probabilities of coagulation defects in ischemic stroke patients are low. The diagnostic yield of coagulation tests may be increased by using tests with the highest specificities and by targeting patients with clinical or historical features that increase pretest probability. Consideration of these data might lead to more rational ordering of tests and an associated cost savings.

We investigated the relationship between transcranial Doppler (TCD) pulsatility index (PI) and central aortic pressure by measurement of the aortic augmentation index (AIx).We enrolled 148 consecutive patients with a diagnosis of acute ischemic stroke. Patients were eligible for the study if they experienced their first ischemic stroke within the preceding 7 days and were 45 years of age or older. At Day 7 (±2) after stroke onset, TCD studies were performed and AIx was measured by applanation tonometry on the same days.The mean age was 66.3 (47-90) years and 37.8% were women. The mean middle cerebral artery (MCA) PI was significantly related with age (r =.361), hypertension (r = .184), peripheral systolic blood pressure (SBP; r = .211), peripheral pulse pressure (PP; r = .396), aortic SBP (r = .184), aortic DBP (r = -.181), and aortic PP (r = .371). The basilar artery (BA) PI was significantly related with age (r = .311), peripheral DBP (r = -.267), peripheral PP (r = .358), aortic DBP (r = -.266), and aortic PP (r = .347).TCD PI was significantly related with central aortic pressure, especially PP. The PI in the MCA and BA is closely associated with the pulsatile component of BP in the systemic circulation.

Rural residents are less likely to obtain optimal care for many serious conditions and have poorer health outcomes than those residing in more urban areas. We determined whether rural vs urban residence affected postdischarge medication persistence and 1 year outcomes after stroke.The Adherence eValuation After Ischemic Stroke-Longitudinal (AVAIL) study is a multicenter registry of stroke patients enrolled in 101 hospitals nationwide. Medications were recorded at hospital discharge and again after 3 and 12 months. Persistence was defined as continuation of prescribed discharge medications. Participants were categorized as living in rural or urban settings by cross-referencing home ZIP code with metropolitan statistical area (MSA) designation.Rural patients were younger, more likely to be white, married, smokers, and less likely to be college graduates. There was no difference in stroke type or working status compared to urban patients, and there were minor differences in comorbid conditions. There were no differences based on rural vs urban residence in medication persistence at 3 or 12 months postdischarge and no differences in outcomes of recurrent stroke or rehospitalization at 12 months.Despite differences in patient characteristics, there was no difference in medication persistence or outcomes between rural and urban dwellers after hospitalization for ischemic stroke or transient ischemic attack (TIA).

Objective To measure longitudinal use of stroke prevention medications following stroke hospital discharge. We hypothesized that a combination of patient-, provider-, and system-level factors influence medication-taking behavior. Design Observational cohort design. Setting One hundred six US hospitals participating in the American Heart Association Get With The Guidelines-Stroke program. Patients Two thousand eight hundred eighty-eight patients 18 years or older admitted with ischemic stroke or transient ischemic attack. Main outcome measure Regimen persistence, including use of antiplatelet therapies, warfarin, antihypertensive therapies, lipid-lowering therapies, or diabetes medications, from discharge to 3 months. Reasons for nonpersistence were also ascertained. Results Two thousand five hundred ninety-eight patients (90.0%) were eligible for analysis. At 3 months, 75.5% of subjects continued taking all secondary prevention medications prescribed at discharge. Persistence at 3 months was associated with decreasing number of medication classes prescribed, increasing age, medical history, less severe stroke disability, having insurance, working status, understanding why medications are prescribed and how to refill them, increased quality of life, financial hardship, geographic region, and hospital size. Conclusions One-quarter of stroke patients reported discontinuing 1 or more of their prescribed regimen of secondary prevention medications within 3 months of hospitalization for an acute stroke. Several modifiable factors associated with regimen persistence were identified and could be targets for improving long-term secondary stroke prevention.

Variations in levels of estrogen receptor mRNA were investigated in the medial preoptic nucleus, arcuate nucleus, and ventromedial nucleus of the hypothalamus throughout the phases of the female estrous cycle and compared with those in ovariectomized female and intact male rats. Female Wistar rats were killed during estrus, metestrus, diestrus, or proestrus or 72 h after ovariectomy as were a group of intact male rats. Brains were removed and frozen, and 20-microns cryostat sections were thaw-mounted onto slides and hybridized with a 35S-labeled antisense estrogen receptor probe. Section-mounted slides were processed, apposed to x-ray film, then dipped in liquid emulsion, and quantified. After exposure, estrogen receptor mRNA was detected in several brain regions, including the medial preoptic nucleus, arcuate nucleus, and ventromedial nucleus of the hypothalamus. Estrogen receptor mRNA levels in the medial preoptic nucleus were highest during estrus and metestrus, attenuated at diestrus, and low during proestrus. In contrast, the hybridization signal in the arcuate and ventromedial nuclei was low during estrus and then gradually increased throughout the cycle until it peaked during proestrus. Ovariectomized females exhibited an elevated level of estrogen receptor mRNA in all brain regions investigated. Hybridization signal in male medial preoptic nucleus and ventromedial nucleus was reduced compared with those in both intact and ovariectomized females. Estrogen receptor mRNA levels in the arcuate nucleus were similar to those in intact females, but less than those in ovariectomized animals. The results of these studies demonstrate that estrogen receptor mRNA levels are sexually dimorphic, vary during the estrous cycle, and increase after ovariectomy. Furthermore, these results indicate that the magnitude and direction of change observed during the estrous cycle are region specific and suggest that factors other than endogenous estrogen levels differentially modulate estrogen receptor mRNA expression in the hypothalamus.

P5 Background and Purpose: The NIH Stroke Scale (NIHSS) and the Canadian Neurological Scale (CNS) have been reported to be useful for the retrospective assessment of initial stroke severity. However, the NIHSS requires detailed neurological assessments that may not be reflected in all patient records, potentially limiting its applicability. We assessed the reliability of the retrospective algorithms and the proportions of missing items for the NIHSS and CNS in stroke patients admitted to an academic medical center and 2 community hospitals. Methods: Randomly selected records of patients with ischemic stroke admitted to an academic medical center (AMC, n=20), and community hospitals with (CH1, n=19) and without (CH2, n=20) acute neurological consultative services were reviewed. NIHSS and CNS scores were assigned independently by two neurologists using published algorithms. Inter-rater reliability of the scores was determined with the intraclass correlation coefficient (ICC), and numbers of missing items were tabulated. Results: The ICCs for NIHSS and CNS respectively were 0.93 (95% CI 0.82–1.0) and 0.97 (0.90–1.0) for the AMC, 0.89 (0.75–1.0) and 0.88 (0.73–1.0) for CH1, and 0.48 (0.26–0.70) and 0.78 (0.6–0.96) for CH2. More NIHSS items were missing at CH2 (62%) vs. the AMC (27%) and CH1 (23%, p=0.0001). In comparison, 33%, 0%, and 8%, of CNS items were missing from records from CH2, AMC, and CH1, respectively (p=0.0001). The ICCs for NIHSS missing items were 0.53 (95% CI 0.31–0.75), 0.7 (0.5–0.9), 0.64 (0.42–0.85), for the 3 hospitals, respectively. Conclusions: There are substantial levels of agreement for retrospectively-assigned NIHSS and CNS scores for patients initially evaluated by a neurologist at both an AMC and a CH. However, the proportions of missing items are higher for the NIHSS in each setting, effectively reducing it to the items captured on the CNS, and particularly limiting the NIHSS application in hospitals without acute neurological consultative services.