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Abstract: Children with sickle cell anemia (SCA) are at increased risk of stroke when compared with their age-based counterparts. The Stroke Prevention Trial in Sickle Cell Anemia (STOP) previously demonstrated that with the use of transcranial Doppler ultrasound (TCD; Sickle Stroke Screen) and chronic red cell transfusion, the risk of stroke is reduced by over 90%. The STOP criteria detailed the type and method of measurement required; the time-averaged mean maximum velocity (TAMMV). Unfortunately, it has been difficult to adhere to the appropriate TAMMV measurements. The objectives of this study were to assess the quality of TCD and transcranial Doppler imaging (TCDi) reports to determine the report quality and accuracy. This is a subanalysis of the DISPLACE (Dissemination and Implementation of Stroke Prevention Looking at the Care Environment) study. Over 12 000 TCD/TCDi reports were collected during this study from 28 institutions; 391 TCDs were reviewed for this subanalysis. There were significant variations in the vessels being assessed, the velocities used to define abnormal results, and who was interpreting the scans. In 52% of reports, it was impossible to identify whether the TAMMV was what was measured. Similarly, it was only clear in 42% of reports that the TAMMV was used to interpret the examination as normal/abnormal. Given this inconsistency, we strongly recommend standardization of TCD/TCDi reporting, specialized training for those performing and interpreting the scans in the use of TCD/TCDi in patients with SCA, internal quality assurance, and institutional quality improvement work to ensure appropriate use of this potentially lifesaving technology., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: Functional task performance requires proper control of both movement and force generation in three-dimensional space, especially for the hand. Control of force in three dimensions, however, is not explicitly treated in current physical rehabilitation. To address this gap in treatment, we have developed a tool to provide visual feedback on three-dimensional finger force. Our objective is to examine the effectiveness of training with this tool to restore hand function in stroke survivors., Methods: Double-blind randomized controlled trial. All participants undergo 18 1-h training sessions to practice generating volitional finger force of various target directions and magnitudes. The experimental group receives feedback on both force direction and magnitude, while the control group receives feedback on force magnitude only. The primary outcome is hand function as measured by the Action Research Arm Test. Other outcomes include the Box and Block Test, Stroke Impact Scale, ability to direct finger force, muscle activation pattern, and qualitative interviews., Discussion: The protocol for this clinical trial is described in detail. The results of this study will reveal whether explicit training of finger force direction in stroke survivors leads to improved motor control of the hand. This study will also improve the understanding of neuromuscular mechanisms underlying the recovery of hand function., Trial Registration: ClinicalTrials.gov NCT03995069 . Registered on June 21, 2019., (© 2022. The Author(s).)

Background and Purpose: In the general population, Black adults are less likely than White adults to have controlled blood pressure (BP), and when not controlled, they are at greater risk for stroke compared with White adults. High BP is a major modifiable risk factor for recurrent stroke, but few studies have examined racial differences in BP control among stroke survivors., Methods: We used data from the REGARDS study (Reasons for Geographic and Racial Differences in Stroke) to examine disparities in BP control between Black and White adults, with and without a history of stroke. We studied participants taking antihypertensive medication who did and did not experience an adjudicated stroke (n=306 and 7693 participants, respectively) between baseline (2003-2007) and a second study visit (2013-2016). BP control at the second study visit was defined as systolic BP <130 mm Hg and diastolic BP <80 mm Hg except for low-risk adults ≥65 years of age (ie, those without diabetes, chronic kidney disease, history of cardiovascular disease, and with a 10-year predicted atherosclerotic cardiovascular disease risk <10%) for whom BP control was defined as systolic BP <130 mm Hg., Results: Among participants with a history of stroke, 50.3% of White compared with 39.3% of Black participants had controlled BP. Among participants without a history of stroke, 56.0% of White compared with 50.2% of Black participants had controlled BP. After multivariable adjustment, there was a tendency for Black participants to be less likely than White participants to have controlled BP (prevalence ratio, 0.77 [95% CI, 0.59-1.02] for those with a history of stroke and 0.92 [95% CI, 0.88-0.97] for those without a history of stroke)., Conclusions: There was a lower proportion of controlled BP among Black compared with White adults with or without stroke, with no statistically significant differences after multivariable adjustment.

Stroke prevention guidelines for sickle cell anemia (SCA) recommend transcranial Doppler (TCD) screening to identify children at stroke risk; however, TCD screening implementation remains poor. This report describes results from Part 1 of the 28-site DISPLACE (Dissemination and Implementation of Stroke Prevention Looking at the Care Environment) study, a baseline assessment of TCD implementation rates. This report describes TCD implementation by consortium site characteristics; characteristics of TCDs completed; and TCD results based on age. The cohort included 5247 children with SCA, of whom 5116 were eligible for TCD implementation assessment for at least 1 study year. The majority of children were African American or Black, non-Hispanic and received Medicaid. Mean age at first recorded TCD was 5.9 and 10.5 years at study end. Observed TCD screening rates were unsatisfactory across geographic regions (mean 49.9%; range: 30.9% to 74.7%) independent of size, institution type, or previous stroke prevention trial participation. The abnormal TCD rate was 2.9%, with a median age of 6.3 years for first abnormal TCD result. Findings highlight real-world TCD screening practices and results from the largest SCA cohort to date. Data informed the part 3 implementation study for improving stroke screening and findings may inform clinical practice improvements., Competing Interests: Dr J.K. reports receiving grants (R01HL133896, U01HL133990) from the National Institutes of Health (NIH), the Health Resources and Services Administration and the Centers for Disease Control. She has served as a Principal Investigator on studies funded by Novartis Pharmaceuticals Corporation, Ironwood Therapeutics Inc., Imara Inc., Baxalta US Inc., Bluebird Bio Inc. She has received honoraria from Novartis Pharmaceuticals Corporation, MEDSCAPE, MD Magazine, Terumo and Bluebird Bio Inc. and travel support for Global Blood Therapeutics. Dr S.P. reports receiving a grant (K23NR017899) from NIH. Dr C.L.M. reports receiving grants (R01HL133896, U01HL133990) from the NIH. Dr R.J.A. reports receiving a grant (R01HL133896) from the NIH and the American Heart Association and consulting honoraria from Global Blood Therapeutics. The remaining authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Purpose: Blacks have a higher burden of post-stroke disability. Factors associated with racial differences in long-term post-stroke disability are not well-understood. Our aim was to assess the long-term racial differences in risk factors associated with stroke recovery., Methods: We examined Health and Retirement Study (HRS) longitudinal interview data collected from adults living with stroke who were aged >50 years during 2000-2014. Analysis of 1,002 first-time, non-Hispanic, Black (210) or White (792) stroke survivors with data on activities of daily living (ADL), fine motor skills (FMS) and gross motor skills (GMS) was conducted. Ordinal regression analysis was used to assess the impact of sex, race, household residents, household income, comorbidities, and the time since having a stroke on functional outcomes., Results: Black stroke survivors were younger compared with Whites (69 ± 10.4 vs 75 ± 11.9). The majority (~65%) of Black stroke survivors were female compared with about 54% White female stroke survivors (P=.007). Black stroke survivors had more household residents (P<.001) and comorbidities (P<.001). Aging, being female, being Black and a longer time since stroke were associated with a higher odds of having increased difficulty in ADL, FMS and/or GMS. Comorbidities were associated with increased difficulty with GMS. Black race increased the impact of comorbidities on ADL and FMS in comparison with Whites., Conclusion: Our data suggest that the effects of aging, sex and unique factors associated with race should be taken into consideration for future studies of post-stroke recovery and therapy., Competing Interests: Competing Interests: None declared., (Copyright © 2020, Ethnicity & Disease, Inc.)

Background: Children with sickle cell anemia (SCA) are at increased risk for stroke. In 2014, the National Heart, Lung, and Blood Institute (NHLBI) developed guidelines for stroke prevention in SCA informed by the Stroke Prevention Trial in Sickle Cell Anemia (STOP) and Optimizing Primary Stroke Prevention in Sickle Cell Anemia (STOP II) trials. The guidelines specify the use of transcranial Doppler (TCD) screening and intervention with chronic red cell transfusions (CRCT) in children with SCA who have TCD indication of high stroke risk. The purpose of this study was to describe real-world practice patterns of stroke risk screening and intervention in sites that participated in the Dissemination and Implementation of Stroke Prevention Looking at the Care Environment (DISPLACE) Consortium., Procedure: Site investigators completed a survey during the formative stages of the study to evaluate their TCD practices relative to the STOP studies. Descriptive statistics and analysis of free-text comments for more complex practices were evaluated., Results: Results suggested universal acceptance of annual TCD screening and initiation of CRCT following an abnormal result among the DISPLACE Consortium, consistent with NHLBI recommendations. However, there was wide variation in methods for conducting TCD screenings (eg, dedicated Doppler vs TCD imaging), classifying TCD results, and actions taken for conditional and inadequate results., Conclusions: Annual TCD screening and initiation of CRCT are critical stroke prevention practices that were universally embraced in the consortium. Additional research would be beneficial for informing clinical practices for areas in which guidelines are absent or unclear., (© 2020 Wiley Periodicals, Inc.)

Importance: African Americans and individuals of African ancestry have a higher risk of stroke compared with non-Hispanic white individuals. Identifying the source of this disparity could provide an opportunity for clinical stroke risk stratification and more targeted therapy. Whether sickle cell trait (SCT) is an indicator of increased risk of ischemic stroke among African Americans is still unclear., Objective: To examine whether SCT is associated with a higher risk of incident ischemic stroke among African Americans., Design, Setting, and Participants: This meta-analysis assessed the association of SCT with the risk of incident ischemic stroke. Four large, prospective, population-based studies with African American cohorts were assessed: Jackson Heart Study (September 1, 2005, through December 31, 2012), Multi-Ethnic Study of Atherosclerosis (July 1, 2002, through December 31, 2012), Reasons for Geographic and Racial Differences in Stroke (January 1, 2003, through December 31, 2014), and Women's Health Initiative (October 1, 1998, through December 31, 2012). Using a Cox proportional hazards regression model adjusted for major stroke risk factors, this study estimated the hazard ratio for incident ischemic stroke associated with SCT. Data analysis was performed from July 10, 2016, to February 2, 2017., Interventions or Exposures: Participants' SCT status determined by polymerase chain reaction assay genotyping or a combination of whole-exome sequencing and imputation., Main Outcomes and Measures: Incident ischemic stroke., Results: This meta-analysis included 19 464 African American individuals (1520 with SCT, 17 944 without SCT, and 620 with ischemic stroke) from 4 studies, with a mean (SD) age of 60.0 (13.0) years (5257 [27.0%] men and 14 207 [73.0%] women). No differences were found in the distribution of risk factors for ischemic stroke comparing participants with and those without SCT at study visit 1 in each cohort. The crude incidence of ischemic stroke was 2.9 per 1000 person-years (95% CI, 2.2-4.0 per 1000 person-years) among those with SCT and 3.2 per 1000 person-years (95% CI, 2.7-3.8 per 1000 person-years) among those without SCT. After stroke risk factors were adjusted for, the hazard ratio of incident ischemic stroke independently associated with SCT in the meta-analysis of all 4 cohorts was 0.80 (95% CI, 0.47-1.35; P = .82). The results of the meta-analysis were similar to those of individual cohorts, in which the results were also similar., Conclusions and Relevance: Sickle cell trait may not be associated with incidence of ischemic stroke among African Americans. The results of this study suggest performing a more thorough clinical evaluation of a stroke patient with SCT rather than assuming that SCT is the etiologic factor for the stroke.

Background: Patients in rural communities lack access to acute stroke therapies. Rapid administration of lytic therapy increases the likelihood of favorable functional outcome in acute ischemic stroke (AIS). At the Medical University of South Carolina (MUSC), we implemented a Web-based telestroke program that allows patients presenting with AIS at a rural hospital to receive expert stroke consultation within minutes. This increases their chances of receiving lytic therapy, and therefore increases the likelihood of good functional outcome., Objectives: Our study aims to provide an update on how our telestroke program had developed and the rate and safety of intravenous (IV) alteplase administration through telestroke., Methods: Data were collected on all patients evaluated through the MUSC Telestroke program from May 2008 through April 2014. Collected data included National Institutes of Health Stroke Scale (NIHSS) on presentation, number of IV alteplase administrations, number of patients transferred to MUSC, number of mechanical thrombectomies performed on transferred patients, rate of symptomatic intracerebral hemorrhages (sICHs), and discharge location., Results: A total of 7,694 consults were performed during the study period. Of them 3,795 (49.2%) patients were diagnosed with ischemic stroke, of those 1,324 (34.8%) received IV alteplase. A total of 1,282 patients were transferred to MUSC for further care. From November 2014 to April 2016, 56 patients received mechanical thrombectomy. sICH occurred in 33 patients who received alteplase, and in 5 patients receiving a combination of IV and intraarterial thrombolysis. Over the study period, the number of participating sites increased from 6 to 19 sites. The percentage of transfers to MUSC decreased from 36% to 14%., Conclusions: Our study shows that our telestroke program had evolved over time to involve more sites throughout the state of South Carolina. Post-IV alteplase sICH was low and within the expected range.

Background and Purpose: The recommended treatment for ischemic stroke is tPA (tissue-type plasminogen activator). Although sickle cell disease (SCD) represents no known contraindication to tPA, National Heart Lung and Blood Institute of the National Institutes of Health recommended acute exchange transfusion for stroke in SCD, not tPA. Data on safety and outcomes of tPA in patients are needed to guide tPA use in SCD., Methods: We matched patients from the American Heart Association and American Stroke Association Get With The Guidelines-Stroke registry with SCD to patients without SCD and compared usage, complications, and discharge outcomes after tPA. Multivariable logistic regression models using generalized estimating equations were used to assess outcomes., Results: From 2 016 652 stroke patients admitted to Get With The Guidelines-Stroke sites in the United States, 832 SCD and 3328 non-SCD controls with no differences in admission National Institutes of Health Stroke Scale or blood pressure were identified. Neither the fraction receiving thrombolytic therapy (8.2% for SCD versus 9.4% non-SCD) nor symptomatic intracranial hemorrhage (4.9% of SCD versus 3.2% non-SCD; P =0.4502) was different. There was no difference in a prespecified set of outcome measures for those with SCD compared with controls., Conclusions: Coexistent SCD had no significant impact on the safety or outcome of thrombolytic therapy in acute ischemic stroke. Although the sample size is relatively small, these data suggest that adults with SCD and acute ischemic stroke should be treated with thrombolysis, if they otherwise qualify. Addition studies, however, should track the intracranial hemorrhage rate and provide information on other SCD-related care such as transfusion., (© 2017 American Heart Association, Inc.)

In children with Sickle Cell Disease, the combination of risk stratification with Transcranial Doppler Ultrasound (TCD) and selective chronic red cell transfusion (CRCT-the STOP Protocol) is one of the most effective stroke prevention strategies in medicine. How fully it is being implemented is unclear. Nineteen of 26 sites that conducted the two pivotal clinical trials (STOP and STOP II) participated in Post STOP, a comprehensive medical records review assessing protocol implementation in the 10-15 years since the trials ended. Professional abstractors identified medical records in the Post STOP era in 2851 (74%) of the 3,840 children who took part in STOP and/or STOP II, and documented TCD rescreening, maintenance of CRCT in those at risk, and stroke. Among 1,896 children eligible for TCD rescreening (target group), evidence of any rescreening was found in 1,090 (57%). There was wide site variation in TCD rescreening ranging from 18% to 91% of eligible children. Both younger age and having a conditional TCD during STOP/II were associated with a higher likelihood of having a TCD in Post STOP. Sixty eight new abnormal, high risk cases were identified. Despite clear evidence of benefit the STOP protocol is not fully implemented even at experienced sites. Site variation suggests that system improvements might remove barriers to implementation and result in even greater reduction of ischemic stroke in children with SCD. Am. J. Hematol. 91:1191-1194, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Introduction: The use of mechanical thrombectomy for the treatment of acute ischemic stroke has significantly advanced over the last 5 years. Few data are available comparing the cost and clinical and angiographic outcomes associated with available techniques. The aim of this study is to compare the cost and efficacy of current endovascular stroke therapies., Methods: A single-center retrospective review was performed of the medical record and hospital financial database of all ischemic stroke cases admitted from 2009 to 2013. Three discrete treatment methodologies used during this time were compared: traditional Penumbra System (PS), stent retriever with local aspiration (SRLA) and A Direct Aspiration first Pass Technique (ADAPT). Statistical analyses of clinical and angiographic outcomes and costs for each group were performed., Results: 222 patients (45% men) underwent mechanical thrombectomy. Successful revascularization was defined as Thrombolysis In Cerebral Infarction (TICI) 2b/3 flow, which was achieved in 79% of cases with PS, 83% of cases with SRLA, and 95% of cases with ADAPT. The average total cost of hospitalization for patients was $51,599 with PS, $54,700 with SRLA, and $33 ,11 with ADAPT (p<0.0001). Average times to recanalization were 88 min with PS, 47 min with SRLA, and 37 min with ADAPT (p<0.0001). Similar rates of good functional outcomes were seen in the three groups (PS 36% vs SRLA 43% vs ADAPT 47%; p=0.4)., Conclusions: The ADAPT technique represents the most technically successful yet cost-effective approach to revascularization of large vessel intracranial occlusions., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Hypercoagulability in sickle cell disease (SCD) is associated with multiple SCD phenotypes, association with stroke risk has not been well described. We hypothesized that serum levels of biomarkers of coagulation activation correlate with high transcranial Doppler ultrasound velocity and decreases with blood transfusion therapy in SCD patients. Stored serum samples from subjects in the Stroke Prevention in Sickle Cell Anemia (STOP) trial were analyzed using ELISA and protein multiplexing techniques. 40 subjects from each treatment arm (Standard Care [SC] and Transfusion [Tx]) at three time points--baseline, study exit and one year post-trial and 10 each of age matched children with SCD but normal TCD (SNTCD) and with normal hemoglobin (HbAA) were analyzed. At baseline, median vWF, TAT and D-dimer levels were significantly higher among STOP subjects than either HbAA or SNTCD. At study exit, median hemoglobin level was significantly higher while median TCD velocity was significantly lower in Tx compared to SC subjects. Median vWF (409.6 vs. 542.9 μg/ml), TAT (24.8 vs. 40.0 ng/ml) and D-dimer (9.2 vs. 19.1 μg/ml) levels were also significantly lower in the Tx compared to the SC group at study exit. Blood levels of biomarkers coagulation activation/thrombin generation correlated positively with TCD velocity and negatively with number of blood transfusions. Biomarkers of coagulation activation/thrombin generation were significantly elevated in children with SCD, at high risk for stroke. Reduction in levels of these biomarkers correlated with reduction in stroke risk (lower TCD velocity), indicating a possible role for hypercoagulation in SCD associated stroke.

Background: Telestroke extends stroke expertise to underserved hospitals and facilitates treatment with tissue plasminogen activator (tPA). We investigated the variability in tPA treatment rates across 2 large telestroke networks-consisting of hubs at Georgia Regents Medical Center (GRMC) and Medical University of South Carolina (MUSC) and their affiliated spoke hospitals-to identify spoke-related factors predictive of greater tPA use., Methods: Observational study of tPA treatment rate at 32 spoke hospitals within the GRMC and MUSC telestroke networks. Spokes were characterized by primary stroke center status, local stroke nurse coordinator, local neurology support, hospital size, post-tPA management strategy, whether the spoke hospitals paid to participate in the network, and whether the hub or the spoke hospital initially proposed the telemedicine linkage for consultations with a remote stroke specialist. Primary outcome was tPA treatment rate adjusted for emergency department (ED) volume., Results: There was substantial variation in the adjusted tPA rate across spokes (range, .85-8.74 administrations/10(4) ED visits/year). Only spokes with a stroke nurse coordinator (4.75/10(4) ED visits/year versus 2.84/10(4) ED visits/year, P = .03) were associated with higher tPA use., Conclusions: The application of telestroke has variable results on tPA delivery in spoke hospitals. However, the presence of a stroke nurse coordinator at the spoke facilitated treatment of ischemic stroke cases with tPA., (Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

To optimize the translation of clinical trial evidence that antihypertensive treatment reduces recurrent stroke risk into clinical practice, it is important to assess the frequency of long-term antihypertensive drug persistence after stroke and identify the factors associated with low persistence. Structured telephone interviews to determine antihypertensive regimen persistence 1-year post-stroke hospitalization were conducted in 270 stroke survivors, of which 212 (78.5%) were discharged on antihypertensive therapy (two thirds on >1 drug class). Continued use of any antihypertensive agent at 1 year of follow-up was relatively high (87.3%); however, persistence on all or two or more drug classes prescribed at discharge was relatively low (38.7%). Continued use varied by drug class, with the highest rates among angiotensin-converting enzyme inhibitor (69.1%) and the lowest rates among diuretic (24.4%) users. Black patients (adjusted odds ratio, 0.35; 95% confidence interval, 0.16-0.78) and those with a high comorbidity burden (adjusted odds ratio , 0.39; 95% confidence interval, 0.18-0.86) were less likely to exhibit persistence on prescribed treatments 1-year post-stroke hospitalization. These results indicate the need for further study to identify appropriate persistence of antihypertensive therapies for secondary stroke prevention and to investigate reasons for racial disparities in persistence on prescribed treatments in a real-world clinical setting., (Copyright © 2014 Wiley Periodicals, Inc.)

Background: The use of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9) diagnostic codes can identify racial disparities in ischemic stroke hospitalizations; however, inclusion of revascularization procedure codes as acute stroke events may affect the magnitude of the risk difference. This study assesses the impact of excluding revascularization procedure codes in the ICD-9 definition of ischemic stroke, compared with the traditional inclusive definition, on racial disparity estimates for stroke incidence and recurrence., Methods: Patients discharged with a diagnosis of ischemic stroke (ICD-9 codes 433.00-434.91 and 436) were identified from a statewide inpatient discharge database from 2010 to 2012. Race-age specific disparity estimates of stroke incidence and recurrence and 1-year cumulative recurrent stroke rates were compared between the routinely used traditional classification and a modified classification of stroke that excluded primary ICD-9 cerebral revascularization procedures codes (38.12, 00.61, and 00.63)., Results: The traditional classification identified 7878 stroke hospitalizations, whereas the modified classification resulted in 18% fewer hospitalizations (n = 6444). The age-specific black to white rate ratios were significantly higher in the modified than in the traditional classification for stroke incidence (rate ratio, 1.50; 95% confidence interval [CI], 1.43-1.58 vs. rate ratio, 1.24; 95% CI, 1.18-1.30, respectively). In whites, the 1-year cumulative recurrence rate was significantly reduced by 46% (45-64 years) and 49% (≥ 65 years) in the modified classification, largely explained by a higher rate of cerebral revascularization procedures among whites. There were nonsignificant reductions of 14% (45-64 years) and 19% (≥ 65 years) among blacks., Conclusions: Including cerebral revascularization procedure codes overestimates hospitalization rates for ischemic stroke and significantly underestimates the racial disparity estimates in stroke incidence and recurrence., (Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: Response to stroke symptoms and the use of 911 can vary by race/ethnicity. The quickness with which a patient responds to such symptoms has implications for the outcome and treatment. We sought to examine a sample of patients receiving a Remote Evaluation of Acute isCHemic stroke (REACH) telestroke consult in South Carolina regarding their awareness and perception of stroke symptoms related to the use of 911 and to assess possible racial/ethnic disparities., Methods: As of September 2013, 2325 REACH telestroke consults were conducted in 13 centers throughout South Carolina. Telephone surveys assessing use of 911 were administered from March 2012-January 2013 among 197 patients receiving REACH consults. Univariate and multivariate logistic regression was performed to assess factors associated with use of 911., Results: Most participants (73%) were Caucasian (27% were African-American) and male (54%). The mean age was 66 ± 14.3 years. Factors associated with use of 911 included National Institutes of Health Stroke Scale scores >4 (odds ratio [OR], 5.4; 95% confidence interval [CI], 2.63-11.25), unknown insurance which includes self-pay or not charged (OR, 2.90; 95% CI, 1.15-7.28), and perception of stroke-like symptoms as an emergency (OR, 4.58; 95% CI, 1.65-12.67). African-Americans were significantly more likely than Caucasians to call 911 (62% vs. 43%, P = .02)., Conclusions: African-Americans used 911 at a significantly higher rate. Use of 911 may be related to access to transportation, lack of insurance, or proximity to the hospital although this information was not available. Interventions are needed to improve patient arrival times to telemedicine equipped emergency departments after stroke., (Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

The Stroke With Transfusions Changing to Hydroxyurea (SWiTCH) trial compared standard (transfusions/chelation) to alternative (hydroxyurea/phlebotomy) treatment to prevent recurrent stroke and manage iron overload in children chronically transfused over 7 years before enrollment. Standardized brain magnetic resonance imaging/magnetic resonance angiography (MRA) and transcranial Doppler (TCD) exams were performed at entry and exit, with a central blinded review. A novel MRA vasculopathy grading scale demonstrated frequent severe baseline left/right vessel stenosis (53%/41% ≥Grade 4); 31% had no vessel stenosis on either side. Baseline parenchymal injury was prevalent (85%/79% subcortical, 53%/37% cortical, 50%/35% subcortical and cortical). Most children had low or uninterpretable baseline middle cerebral artery TCD velocities, which were associated with worse stenoses (incidence risk ratio [IRR] = 5.1, P ≤ .0001 and IRR = 4.1, P < .0001) than normal velocities; only 2% to 12% had any conditional/abnormal velocity. Patients with adjudicated stroke (7) and transient ischemic attacks (19 in 11 standard/8 alternative arm subjects) had substantial parenchymal injury/vessel stenosis. At exit, 1 child (alternative arm) had a new silent infarct, and another had worse stenosis. SWiTCH neuroimaging data document severe parenchymal and vascular abnormalities in children with SCA and stroke and support concerns about chronic transfusions lacking effectiveness for preventing progressive cerebrovascular injury. The novel SWiTCH vasculopathy grading scale warrants validation testing and consideration for use in future clinical trials. This trial was registered at www.clinicaltrials.gov as #NCT00122980., (© 2014 by The American Society of Hematology.)

Background and Purpose: Mounting evidence points to a decline in stroke incidence. However, little is known about recent patterns of stroke hospitalization within the buckle of the stroke belt. This study aims to investigate the age- and race-specific secular trends in stroke hospitalization rates, inpatient stroke mortality rates, and related hospitalization charges during the past decade in South Carolina., Methods: Patients from 2001 to 2010 were identified from the State Inpatient Hospital Discharge Database with a primary discharge diagnosis of stroke (International Classification of Diseases, Ninth Revision codes: 430-434, 436, 437.1). Age- and race-stroke-specific hospitalization rates, hospital charges, charges associated with racial disparity, and 30-day stroke mortality rates were compared between blacks and whites., Results: Of the 84,179 stroke hospitalizations, 31,137 (37.0%) were from patients aged<65 years and 29,846 (35.5%) were blacks. Stroke hospitalization rates decreased in the older population (aged≥65 years) for both blacks and whites (P<0.001) but increased among the younger group (aged<65 years; P=0.004); however, this increase was mainly driven by a 17.3% rise among blacks (P=0.001), with no difference seen among whites (P=0.84). Of hospital charges totaling $2.77 billion, $453.2 million (16.4%) are associated with racial disparity (79.6% from patients aged<65 years). Thirty-day stroke mortality rates decreased in all age-race-stroke-specific groups (P<0.001)., Conclusions: The stroke hospitalization rate increased in the young blacks only, which results in a severe and persistent racial disparity. It highlights the urgent need for a racial disparity reduction in the younger population to alleviate the healthcare burden., (© 2014 American Heart Association, Inc.)

The risk of stroke for a child with SCD is many times greater than that of a healthy child without SCD or heart disease. There is a technique that allows the identification of the children with SCD who have high risk even within this relatively high-risk group. And there is a highly effective preventive treatment. While this would on the surface appear to be a straightforward medical decision, it is not. One must weigh the benefits of preventing permanent brain damage against the risks of infection from transfused blood, iron overload, which is the result of the frequent transfusions, and rare transfusion reactions., (© 2014 American Society of Law, Medicine & Ethics, Inc.)

Background: Patient selection for acute ischemic stroke has been largely driven by time-based criteria, although emerging data suggest that image-based criteria may be useful. The purpose of this study was to directly compare outcomes of patients treated within a traditional time window with those treated beyond this benchmark when CT perfusion (CTP) imaging was used as the primary selection tool., Methods: A prospectively collected database of all patients with acute ischemic stroke who received intra-arterial therapy at the Medical University of South Carolina was retrospectively analyzed, regardless of time from symptom onset. At presentation, CTP maps were qualitatively assessed. Selected patients underwent intra-arterial therapy. Functional outcome according to the modified Rankin scale (mRS) score at about 90 days was documented., Results: 140 patients were included in the study. The median time from symptom onset to groin access was 7.0 h. Overall, 28 patients (20%) had bleeding complications, but only 10 (7.1%) were symptomatic. The average National Institute of Health Stroke Scale (NIHSS) score for patients treated ≤ 7 h from symptom onset was 17.3 and 30.2% had a mRS score of 0-2 at 90 days. Patients treated >7 h from symptom onset had an average NIHSS score of 15.1 and 45.5% achieved a mRS score of 0-2 at 90 days (p=0.104). Patients in the two groups had similar rates of symptomatic intracerebral hemorrhage (8.5% and 5.8%, respectively; p=0.745)., Conclusions: No difference was found in the rates of good functional outcome between patients treated ≤ 7 h and those treated >7 h from symptom onset. These data suggest that imaging-based patient selection is a safe and viable methodology.

Background: The treatment of acute ischemic stroke is traditionally centered on time criteria, although recent evidence suggests that physiologic neuroimaging may be useful. In a multicenter study we evaluated the use of CT perfusion, regardless of time from symptom onset, in patients selected for intra-arterial treatment of ischemic stroke., Methods: Three medical centers retrospectively assessed stroke patients with a National Institute of Health Stroke Scale of ≥ 8, regardless of time from symptom onset. CT perfusion maps were qualitatively assessed. Patients with defined salvageable penumbra underwent intra-arterial revascularization of their occlusion. Functional outcome using the modified Rankin Score (mRS) was recorded., Results: Two hundred and forty-seven patients were selected to undergo intra-arterial treatment based on CT perfusion imaging. The median time from symptom onset to procedure was 6 h. Patients were divided into two groups for analysis: ≤ 8 h and >8 h from symptom onset to endovascular procedure. We found no difference in functional outcome between the two groups (42.8% and 41.9% achieved 90-day mRS ≤ 2, respectively (p=1.0), and 54.9% vs 55.4% (p=1.0) achieved 90-day mRS ≤ 3, respectively). Overall, 48 patients (19.4%) had hemorrhages, of which 20 (8.0%) were symptomatic, with no difference between the groups (p=1.0)., Conclusions: In a multicenter study, we demonstrated similar rates of good functional outcome and intracranial hemorrhage in patients with ischemic stroke when endovascular treatment was performed based on CT perfusion selection rather than time-guided selection. Our findings suggest that physiologic imaging-guided patient selection rather than time for endovascular reperfusion in ischemic stroke may be effective and safe.

Background: The administration of thrombolysis to eligible patients is often limited to centers with expertise. This study was intended to report on the safety and efficacy (in increasing thrombolysis availability) of telemedicine in the acute assessment and treatment of stroke patients presenting to hospitals in distant locations from a designated stroke center., Methods: A web-based telestroke tool (remote evaluation of acute ischemic stroke at Medical University of South Carolina [REACH-MUSC]), was implemented to provide acute stroke care 24 hours per day, 7 days per week to 12 community hospitals in South Carolina., Results: Nine hundred sixty-five consults were performed. Among the 525 patients with a National Institutes of Health Stroke Score >3, 185 (35.7%) were treated with intravenous tissue plasminogen activator (t-PA) alone, 15 (2.9%) received combination of intravenous and intra-arterial thrombolysis/thrombectomy, and 11 (2.1%) were treated with intra-arterial therapy alone. Of those who received intravenous t-PA, 119 (64.3%) were transferred to the hub; the medians (interquartile range) for onset to treatment for the intravenous t-PA and the intravenous t-PA and intra-arterial groups were 152 (range 115-193) minutes and 147 (range 107-179) minutes, respectively. Three patients (1.6%) who received intravenous t-PA alone experienced symptomatic intracerebral hemorrhage. The most common reason for not receiving thrombolysis was patient presentation outside the time window for treatment., Conclusions: Telestroke can have a major impact in increasing thrombolysis rates in remote areas from specialized centers, and in particular in areas where t-PA is underutilized., (Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Stroke is a devastating complication of sickle cell anemia (SCA), occurring in 11% of patients before age 20 years. Previous studies of sibling pairs have demonstrated a genetic component to the development of cerebrovascular disease in SCA, but few candidate genetic modifiers have been validated as having a substantial effect on stroke risk. We performed an unbiased whole-genome search for genetic modifiers of stroke risk in SCA. Genome-wide association studies were performed using genotype data from single-nucleotide polymorphism arrays, whereas a pooled DNA approach was used to perform whole-exome sequencing. In combination, 22 nonsynonymous variants were identified and represent key candidates for further in-depth study. To validate the association of these mutations with the risk for stroke, the 22 candidate variants were genotyped in an independent cohort of control patients (n = 231) and patients with stroke (n = 57) with SCA. One mutation in GOLGB1 (Y1212C) and another mutation in ENPP1 (K173Q) were confirmed as having significant associations with a decreased risk for stroke. These mutations were discovered and validated by an unbiased whole-genome approach, and future studies will focus on how these functional mutations may lead to protection from stroke in the context of SCA.

Background and Purpose: Despite being the gold standard technique for stroke assessment, conventional diffusion MRI provides only partial information about tissue microstructure. Diffusional kurtosis imaging is an advanced diffusion MRI method that yields, in addition to conventional diffusion information, the diffusional kurtosis, which may help improve characterization of tissue microstructure. In particular, this additional information permits the description of white matter (WM) in terms of WM-specific diffusion metrics. The goal of this study is to elucidate possible biophysical mechanisms underlying ischemia using these new WM metrics., Methods: We performed a retrospective review of clinical and diffusional kurtosis imaging data of 44 patients with acute/subacute ischemic stroke. Patients with a history of brain neoplasm or intracranial hemorrhages were excluded from this study. Region of interest analysis was performed to measure percent change of diffusion metrics in ischemic WM lesions compared with the contralateral hemisphere., Results: Kurtosis maps exhibit distinct ischemic lesion heterogeneity that is not apparent on apparent diffusion coefficient maps. Kurtosis metrics also have significantly higher absolute percent change than complementary conventional diffusion metrics. Our WM metrics reveal an increase in axonal density and a larger decrease in the intra-axonal (Da) compared with extra-axonal diffusion microenvironment of the ischemic WM lesion., Conclusions: The well-known decrease in the apparent diffusion coefficient of WM after ischemia is found to be mainly driven by a significant drop in the intra-axonal diffusion microenvironment. Our results suggest that ischemia preferentially alters intra-axonal environment, consistent with a proposed mechanism of focal enlargement of axons known as axonal swelling or beading.

Sickle cell anemia (SCA) associated cerebrovascular disease includes vascular remodeling, abnormal cerebral blood flow (CBF) and infarction. We studied the relationships between plasma brain derived neurotropic factor (BDNF), platelet derived growth factors (PDGF-AA and -AB/BB) and high trans-cranial Doppler (TCD) velocity, an indication of CBF velocity. Baseline plasma samples from 39 children (19 SCA with abnormal/high TCD [SATCD], 13 SCA with normal TCD [SNTCD] and 7 healthy non-SCA), were assayed for BDNF, PDGF-AA and -AB/BB plus 11 other cytokines. The sensitivity, specificity and usefulness of these biomarkers for stroke prediction was investigated. All subject groups were of similar age and gender distribution. Mean BDNF was significantly higher among SATCD than SNTCD (p=0.004) as was mean PDGF-AA (p=0.001). Similarly, mean PDGF-AA was higher among SCA subjects who developed stroke than those who did not (p=0.012). Elevated BDNF and PDGF-AA were good predictors of the presence of abnormally high CBF velocity and were both associated with severity of anemia. Elevated PDGF-AA predicted risk for stroke development. Stroke incidence and high TCD velocity were associated with elevated BDNF and PDGF-AA. These findings suggest a role for BDNF and PDGF-AA in the patho-physiological mechanism of cerebrovascular disease in SCA., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Traditional treatment in acute ischemic stroke is based on time criteria when administering intravenous and intra-arterial therapies. However, recent evidence suggests that image-based criteria may be useful for selecting patients for intra-arterial interventions. The use of CT perfusion (CTP)-based criteria, regardless of time from symptom onset, in patient selection for intra-arterial treatment of ischemic stroke was assessed., Methods: Patients with ischemic stroke who presented to the emergency department at the Medical University of South Carolina with a National Institute of Health Stroke Scale score of ≥ 8, regardless of time from symptom onset, were assessed retrospectively. CTP maps were qualitatively assessed for the presence of penumbra and infarction. Selected patients underwent mechanical aspiration of their occlusion using the Penumbra system. Functional outcome was then recorded using the modified Rankin scale (mRS) at 90 days or the closest follow-up to 90 days., Results: 53 patients were included in the study. The median time from symptom onset to groin vascular access was 6.3 h. Eight patients (15%) had bleeding complications including subarachnoid hemorrhage, parenchymal hemorrhage and intraventricular hemorrhage. After CTP-based selection, the patients were divided into two groups for analysis: ≤6 h and >6 h from symptom onset to endovascular procedure. No difference was found in functional outcome between the two groups (38.5% and 40.7% achieved 90-day mRS ≤2, respectively (p=1.0) and 57.7% and 51.9% achieved 90-day mRS ≤3, respectively (p=0.785)). There was no difference in the rate of intracranial hemorrhage between the two groups (11.5 vs 18.5, p=0.704)., Conclusion: This study demonstrated similar rates of good functional outcome and intracranial hemorrhage in patients with ischemic stroke when endovascular treatment was performed based on CTP selection rather than time-guided selection. These findings suggest that endovascular reperfusion in ischemic stroke may be effective and safe, and may allow patient selection not solely based on time from symptom onset.

Background: Stroke is a major complication of sickle cell disease (SCD). In an era of chronic red cell transfusions for stroke prophylaxis in children and greater life expectancy, nationwide data on stroke rates among pediatric and adult patients with SCD are scarce. We evaluated recent time trends in stroke hospitalization among children (0-17 years) and adults (>17 years) with SCD in the United States., Methods: Data were obtained from the Nationwide Inpatient Sample. Pediatric (n=26,380) and adult (n=9,638,507) patients admitted to hospitals between 1997 and 2006 with a primary stroke discharge diagnosis (identified by the International Classification of Diseases, Ninth Revision procedure codes) were included. Time trends in the proportion of stroke patients with SCD were computed., Results: Pediatric stroke patients with co-morbid SCD constituted 8.7% in 1997 vs. 4.8% in 2006 (p=0.04), with 81 fewer actual hospitalizations. Adult stroke patients with SCD were 0.3% in 1997 vs. 0.5% in 2006 (p=0.01), with 157 more actual hospitalizations. Factors that changed substantially and significantly across the decade among pediatric stroke patients with SCD included a drop in ischemic stroke type (74.2% vs. 56.3%) and a rise in comorbid hypertension (1.5% vs. 11.5%), while among adult stroke patients with SCD there was a rise in other stroke type (20.4% vs. 35.6%)., Conclusions: In an era of increasing prophylactic red cell transfusions, the proportion of SCD diagnoses among pediatric stroke patients significantly decreased in the United States. The rise in SCD diagnoses among adult stroke patients is possibly due to a cohort effect, but further study is needed., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Chronic blood transfusion (CBT) is currently the standard of care for primary and secondary stroke prevention in children with sickle cell anemia (SCA). However, the effect of CBT on cerebrovascular pathology is not well known., Methods: We reviewed children with SCA receiving CBT for abnormal transcranial Doppler (TCD) [n=12] or cerebrovascular accident (CVA) [n=22]. Baseline cerebral magnetic resonance imaging (MRI) and magnetic resonance angiogram (MRA) were compared with the most recent scans available for each patient and independently scored by a neuroradiologist., Results: Thirty-four patients with a mean age of 6.5years at the time of baseline MRI/MRA were studied. Average elapsed time from baseline to most recent scans was 7.3years. Overall, patients experienced worsening vasculopathy, as measured by mean increases in their baseline MRI and MRA scores of +0.76 and +1.03. There was a significant difference in the mean change of MRI/MRA scores between patients who had CVA and abnormal TCD (MRI; +1.23 vs. -0.08, p=0.001 and MRA; +1.54 vs. +0.08, p=0.02). Patients with abnormal baseline MRA had worsening scores compared to those with normal baseline MRA (54% vs. 9.5%, p=0.01). Also, patients who had CVA were more likely to have an abnormal baseline MRA and worsening scores compared to abnormal TCD patients., Conclusion: We show that children with CVA experience progression of cerebral vasculopathy despite CBT. In contrast, CBT for abnormal TCD confers protection against the development and/or progression of cerebral vasculopathy. This effect appears to be real given our large cohort of patients with longer follow up as compared to previous studies., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Stroke is a devastating complication of sickle cell anemia (SCA), affecting 5% to 10% of patients before adulthood. Several candidate genetic polymorphisms have been proposed to affect stroke risk, but few have been validated, mainly because previous studies were hampered by relatively small sample sizes and the absence of additional patient cohorts for validation testing. To verify the accuracy of proposed genetic modifiers influencing stroke risk in SCA, we performed genotyping for 38 published single nucleotide polymorphisms (SNPs), as well as α-thalassemia, G6PD A(-) variant deficiency, and β-globin haplotype in 2 cohorts of children with well-defined stroke phenotypes (130 stroke, 103 nonstroke). Five polymorphisms had significant influence (P < .05): SNPs in the ANXA2, TGFBR3, and TEK genes were associated with increased stroke risk, whereas α-thalassemia and a SNP in the ADCY9 gene were linked with decreased stroke risk. Further investigation at these genetic regions may help define mutations that confer stroke risk or protection in children with SCA.

Background: Children with sickle cell disease (SCD) and abnormal transcranial Doppler (TCD) ultrasonography have a high risk of stroke, but this risk is greatly reduced when chronic transfusion therapy is administered. The change in TCD velocities during chronic transfusion therapy and rate and frequency of normalization of TCD findings have not been studied extensively., Procedures: Using data from children with SCD enrolled as potential subjects in the Optimizing Primary Stroke Prevention in Sickle Cell Anemia (STOP 2) trial, we characterized the change in TCD velocities on transfusion therapy and identified predictors of developing a normal TCD., Results: Among 88 children with serial TCD data after starting transfusions for abnormal TCD 46 (52%) converted to normal TCD after a mean of 4.3 months (median 3.0; range 0.85-14.3 months) of transfusions. TCD studies remained abnormal in 19/88 (21.6%) after a mean of 2.4 years of transfusion. The median TCD velocity was lowered by 38 cm/sec within 3 months of initiating transfusions, followed by a more gradual decline then stabilization of velocities, although with significant individual variation. Factors associated with conversion to normal TCD included lower initial TCD velocity, younger age, and higher pre-transfusion hemoglobin level during transfusion therapy., Conclusion: Younger children with higher pre-transfusion hemoglobin levels and lower abnormal TCD velocities are most likely to have rapid normalization of TCD on transfusions. Long-term follow-up of children with persistently abnormal exams or worsening velocities on transfusion is needed to determine if these children are at higher risk of stroke., (Copyright © 2010 Wiley-Liss, Inc.)

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., Conclusions: Extensive evidence identifies a variety of specific factors that increase the risk of a first stroke and that provide strategies for reducing that risk.

Background and Purpose: Ischemic stroke lesion volumes have proven difficult to analyze due to the extremely skewed shape of their underlying distribution. We introduce an extension of generalized linear models, beta regression, as a possible method of modeling extremely skewed distributions as evidenced in ischemic stroke lesion volumes., Methods: The NINDS rt-PA clinical trials measured ischemic stroke lesion volume as a secondary trial outcome. Three-month lesion volumes from these trials were analyzed using beta regression. A multi-variable regression model associating explanatory variables with ischemic stroke lesion volumes was constructed using accepted model building strategies and compared with the previously published volumetric analysis., Results: Beta regression produced a similar model when compared to the previous analysis published by the study group. All previously identified variables of importance were detected in the model building process. The age by treatment interaction described in previous studies was also found in this analysis, confirming the strong effect age has on stroke outcomes. Further, a treatment effect was elicited in terms of odds ratios, yielding a previously unknown quantification of the effect of rt-PA on lesion volumes., Conclusions: Beta regression proved adept in modeling ischemic stroke lesions and offered the interpretation of covariates in terms of odds ratios. Beta regression is seen as a legitimate alternative to analyze ischemic stroke volumes., (Copyright © 2011 S. Karger AG, Basel.)

The aim of this updated statement is to provide comprehensive and timely evidence-based recommendations on the prevention of ischemic stroke among survivors of ischemic stroke or transient ischemic attack. Evidence-based recommendations are included for the control of risk factors, interventional approaches for atherosclerotic disease, antithrombotic treatments for cardioembolism, and the use of antiplatelet agents for noncardioembolic stroke. Further recommendations are provided for the prevention of recurrent stroke in a variety of other specific circumstances, including arterial dissections; patent foramen ovale; hyperhomocysteinemia; hypercoagulable states; sickle cell disease; cerebral venous sinus thrombosis; stroke among women, particularly with regard to pregnancy and the use of postmenopausal hormones; the use of anticoagulation after cerebral hemorrhage; and special approaches to the implementation of guidelines and their use in high-risk populations.

Objective: This study examines the risk of recurrent stroke, myocardial infarction (MI), vascular death, or all-cause death after hospitalized stroke in South Carolina., Methods: Patients with a primary diagnosis of stroke discharged from the year 2002 were identified from the state hospital discharge database. Kaplan-Meier estimates of recurrent stroke, MI, vascular death, all-cause death, and composite events were calculated at 1 month, 6 months, 1 year, 2 years, 3 years, and 4 years. Prognostic factors were assessed with multivariate Cox proportional hazard models., Results: The search strategy identified 10,399 patients in 2002. The Kaplan-Meier estimate of cumulative risk at 1 month, 6 months, 1 year, 2 years, 3 years, and 4 years for recurrent stroke is 1.8%, 5.0%, 8.0%, 12.1%, 15.2%, and 18.1%; MI, 0.3%, 1.0%, 2.1%, 3.7%, 5.0%, and 6.2%; all-cause death, 14.6%, 20.6%, 24.5%, 30.9%, 36.2%, and 41.3%; vascular death, 11.4%, 14.8%, 17.1%, 20.7%, 23.8%, and 26.7%; and composite events of recurrent stroke, MI, or vascular death 13.6%, 19.5%, 24.7%, 31.6%, 36.8%, and 41.3%. The hazard ratio for composite events (recurrent stroke, MI, or death) increases with age (1.38, 1.35-1.41), is 1.12 (1.05-1.19) for African Americans compared to Caucasians, is 1.67 (1.57-1.77) for patients with a higher comorbidity index (> or = 2 vs <2), and is 1.34 (1.28-1.39) for patients with subarachnoid hemorrhage or intracerebral hemorrhage compared with ischemic stroke., Conclusions: These findings suggest there is room for further improvement in secondary stroke prevention in South Carolina.

Background: Transcranial Doppler ultrasonography (TCD) is used to predict stroke risk in children with sickle cell anemia (SCA), but has not been adequately studied in children under age 2 years., Procedure: TCD was performed on infants with SCA enrolled in the BABY HUG trial. Subjects were 7-17 months of age (mean 12.6 months). TCD examinations were successfully performed in 94% of subjects (n = 192)., Results: No patient had an abnormal TCD as defined in the older child (time averaged maximum mean TAMM velocity > or =200 cm/sec) and only four subjects (2%) had velocities in the conditional range (170-199 cm/sec). TCD velocities were inversely related to hemoglobin (Hb) concentration and directly related to increasing age., Conclusion: Determination of whether the TCD values in this very young cohort of infants with SCA can be used to predict stroke risk later in childhood will require analysis of exit TCD's and long-term follow-up, which is ongoing (ClinicalTrials.gov number, NCT00006400)., ((c) 2009 Wiley-Liss, Inc.)

Geographic variation in hypertension is hypothesized as contributing to the stroke belt, an area in the southeastern United States with high stroke mortality. No study has examined hypertension by lifetime exposure to the stroke belt. This association was studied in 19,385 participants in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study, a national population-based cohort. Prevalent hypertension was defined as systolic blood pressure >/=140, diastolic blood pressure >/=90, or use of antihypertensive medications. Stroke belt exposure was assessed by residence at birth, currently, early childhood, adolescence, early adulthood, mid-adulthood, and recently. After adjustment for age, race, sex, physical activity level, body mass index, smoking, alcohol, education, and income, the prevalence of hypertension was significantly more strongly related (P < .0001) with lifetime exposure, adolescence, or early adulthood exposure than exposures at other times. Birthplace and current residence were independently associated with hypertension; however, lifetime, adolescence, or early adulthood exposures were more predictive than joint model with both birthplace and current residence. That adolescence and early adulthood periods are more predictive than residence in the stroke belt for most recent 20-year period suggests community and environmental strategies to prevent hypertension need to start earlier in life., (Copyright 2010 American Society of Hypertension. All rights reserved.)

The pathogenesis of sickle cell disease (HbSS), which has numerous complications including stroke, involves inflammation resulting in alteration of plasma inflammatory protein concentration. We investigated HbSS children with abnormal cerebral blood flow detected by trans-cranial Doppler ultrasound (TCD) who participated in the multi-center stroke prevention (STOP) study, to determine if plasma inflammatory protein concentration is associated with the outcome of stroke. Thirty-nine plasma samples from HbSS participants with elevated TCD who had no stroke, HbSS-NS (n=13) or had stroke, HbSS-S (n=13), HbSS steady-state controls (n=7) and controls with normal hemoglobin, HbAA (n=6), were analyzed simultaneously for 27 circulating inflammatory proteins. Logistic regression and receiver operating characteristics curve analysis of stroke on plasma inflammatory mediator concentration, adjusted for age and gender, demonstrated that interleukin-1beta (IL-1beta) was protective against stroke development (HbSS-NS=19, 17-23, HbSS-S=17, 16-19 pg/mL, median and 25th-75th percentile; odds ratio=0.59, C.I.=0.36-0.96) and was a good predictor of stroke (area under curve=0.852). This result demonstrates a strong association of systemic inflammation with stroke development in HbSS via moderately increased plasma IL-1beta concentration, which is furthermore associated with a decreased likelihood of stroke in HbSS., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Background and Purpose: Racial disparities among US stroke patients have been well documented. However, the extent to which disparities in outcomes vary by age is unclear. This study's goals were to examine the degree of racial disparities in South Carolina between African Americans (AAs) and Caucasian Americans (CAs) in stroke admission rates, hospital charges, and outcomes and to determine whether racial differences varied by age., Methods: From the state hospital discharge database, admissions with a primary diagnosis of stroke discharged from 2002 to 2006 were identified. Age group-specific stroke admission rates, hospital charges, length of stay, intensive care unit utilization, medical complications, and discharge disposition (in-hospital death, discharged home, discharge to rehabilitation facility) were compared between AAs and CAs by multiple-linear or logistic-regression analysis., Results: There were 58 272 stroke admissions during the 5-year period. Stroke admission rates were persistently higher for AAs in all age groups except those > or =85 years old. Hospital charges totaled $1.51 billion; 24.0% ($362.5 million) of this total was attributable to racial disparities, 70.8% ($256.5 million) of which stemmed from the 36.6% of patients <65 years old. Most of the acute outcomes were poorer for AAs compared with CAs across age groups., Conclusions: Racial disparities in stroke admissions are more pronounced in younger age groups and result in significant economic consequences. Although AA stroke patients experienced generally worse acute outcomes than did CAs, these differences appear to be relatively consistent across age groups.

Elevation of blood flow velocity in the large cerebral vessels is known to be of substantial pathophysiologic and prognostic significance in sickle-cell disease (SCD). Its precise cause is not established, but the two obvious proximal mechanisms are obstructive vascular stenosis and hemodynamic dilatation. Here we revisit this distinction by analyzing cerebrovascular reserve capacity. Forty-two patients with SCD underwent measurements of global cerebral blood flow in grey matter by the 133Xe inhalation method during normocapnia and hypercapnia to quantify cerebrovascular reactivity. Cerebral blood flow was significantly higher in SCD patients (120+/-31 ml/100 g/min) than in controls (76+/-20 ml/100 g/min). Reactivity was significantly lower in SCD patients (1.06+/-1.92 versus 2.16+/-1.15%/mm Hg). Stepwise multiple regressions within the SCD sample determined that normocapnic cerebral blood flow was largely predicted by hematocrit (r=-0.59; P<0.0001), whereas hypercapnic reactivity was only predicted by normocapnic flow across all subjects (r=-0.52; P<0.0001). None of the controls, but 24% of the SCD patients showed 'steal' (negative reactivity, chi2=6.05; P<0.02). This impairment of vasodilatory capacity, occurring at perfusion levels above 150 ml/100 g/min, may reflect intrinsic limitations of the human cerebrovascular system and can explain both the elevated blood flow velocities and the high risk of stroke observed in such patients.