Primary Stroke Prevention Research Articles

Cortical Thinning and White Matter Loss in Sickle Cell Anemia Despite Chronic Exchange Transfusion Therapy

Neurovascular complications are a common and major cause of morbidity and mortality in patients with sickle cell disease (SCD). Prior studies have demonstrated cortical thinness (Kim et al. 2016) as well as reduced cerebral volume in children with SCD (Kawadler et al. 2013) when compared to age-matched controls. There is very limited data regarding cerebral volume in adults with SCD. Recently, our group showed that adults with SCD have reduced cerebral volumes when compared to race and age-matched controls (Santini et al. 2021a). A prior prospective study by Nitkunan et al. 2011. demonstrated brain atrophy rate of −0.914%±0.8% in older adults (mean 68 years old) with Small Vessels Disease, which is about twice the rate of healthy controls. Transfusion therapy has been effective in the primary and secondary prevention of strokes and silent infarcts in SCD. Automated erythrocytapheresis (exchange transfusion), in particular, is the most aggressive disease modifying-treatment in SCD, by rapidly diluting sickle hemoglobin and replacing it with normal hemoglobin. We hereby present a case of a 42 -year-old woman with sickle cell anemia (HbSS) who developed accelerated loss of cerebral volume within a three-year period despite chronic exchange transfusion therapy. The patient underwent brain MRI in 2016 and 2019 as part of an NIH-funded, prospective, longitudinal study of the neuroradiological correlates of cognitive dysfunction in SCD. Past medical history is notable for prior right hemispheric stroke for which she was placed on chronic exchange transfusion monthly with the goal of reducing HbS to <30%. T1-weighted images were acquired at 7T MRI using a customized RF coil (Santini et al. 2021b) and with the following parameters: 3D MPRAGE, TE/TI/TR = 2.17/1200/3000 ms, resolution 0.75 mm isotropic, total acquisition time = 5 min. The extent of atrophy was estimated using the longitudinal analysis as part of the Freesurfer package (version 7.1.1) and ITK-snap (version 3.8.0). The pre-exchange HbS was reliably maintained <30% throughout the observation period, during which the patient did not develop new strokes or neurological complications. Unfortunately, in spite of the patient's excellent adherence with the treatment and the achievement of the target HbS values, we observed progression of cerebral atrophy of 2.47% in volume in the hemisphere contralateral to the stroke between the two time points. The differences are also visible in the raw data (Figure 1). Chronic exchange transfusion is the most aggressive preventive treatment for the neurological sequelae of sickle cell disease. This case demonstrates an accelerated brain atrophy, suggesting that this treatment may not be fully protective against progressive cerebral atrophy. Unfortunately, the mechanism of brain atrophy in SCD is not fully understood. More longitudinal studies are needed to assess cortical changes and cerebral volume changes as this can lead to further understanding of their pathophysiology and to the development of therapeutic options to arrest the progression of cerebrovascular disease in this population. [Display omitted] DisclosuresNovelli: Novartis Pharmaceuticals: Consultancy.

Trial in Progress: A Phase 2, Open-Label Study Evaluating the Safety and Efficacy of the PKR Activator Etavopivat (FT-4202) in Patients with Thalassemia or Sickle Cell Disease

Trial in Progress: A Phase 2, Open-Label Study Evaluating the Safety and Efficacy of the PKR Activator Etavopivat (FT-4202) in Patients with Thalassemia or Sickle Cell Disease

Reduced Intensity Hematopoietic Cell Transplantation Improves Cerebral Hemodynamics in Children with Sickle Cell Disease

IntroductionAllogeneic hematopoietic cell transplantation (HCT) is increasingly being utilized in patients with sickle cell disease (SCD) to prevent progressive organ dysfunction, including for primary or secondary stroke prevention. However, outcomes after HCT have mostly been evaluated using broad measures such as overall survival and event free survival with limited direct physiologic evidence of improved cerebral hemodynamics. Cerebral blood flow (CBF; mL blood/100 g tissue/min) is increased in SCD to compensate for chronic anemia, reduced oxygen carrying capacity and to maintain adequate oxygen delivery to the brain tissue. In SCD patients, CBF is inversely associated with intelligence quotient (Strouse JJ, et al. Blood. 2006;108(1):379-381.) and working memory (Prussien KV, et al. Stroke. 2021;52(5):1830-1834.) and has been shown to improve with blood transfusions (Guilliams KP, et al. Blood. 2018;131(9):1012-1021.). Assessment of CBF may help predict long-term neurocognitive outcomes in patients with SCD and assess therapeutic responses to therapies. Additionally, the high metabolic demand of the brain potentially makes assessment of CBF a sensitive predictor of future multiorgan damage in patients with SCD and hence may be useful to help determine eligibility of patients for curative therapies.MethodsWe performed anatomical and hemodynamic magnetic resonance imaging (MRI) of the brain prior to, and at 6 months after HCT in children with SCD undergoing a reduced intensity conditioning based HCT on a clinical study (NCT04362293). All patients received pretransplant conditioning with hydroxyurea, azathioprine, alemtuzumab, thiotepa and low dose total body irradiation (200-400 cGy). All patients received an unmanipulated mobilized peripheral blood derived hematopoietic stem and progenitor cell graft. One patient who received the graft from a haploidentical (HAPLO) donor also received post-transplant cyclophosphamide. Graft versus host disease prophylaxis comprised of sirolimus. A 3-dimensional (3D) T1 sequence was used for gray/white matter segmentation. 3D-pulsed arterial spin labeling (ASL) perfusion imaging (3 mm isotropic) was acquired to measure resting CBF. Mean CBF values were calculated from gray matter. Mean ± standard deviation and median values for various variables are presented.ResultsFour consecutive patients had 2 serial MRIs performed (one before HCT and another 6 months after HCT). Median age at HCT was 14.5 years. Indications for HCT, donor type and whether patients were receiving chronic transfusion therapy (CTT) prior to HCT are indicated in the Table. No patient had prior evidence of overt stroke. All patients engrafted and had >99% donor myeloid chimerism at the time of the post-HCT imaging. Mean pre-HCT hemoglobin was 8.7 ± 0.8 g/dL (median 8.6 g/dL) and it increased to 12.5 ± 2.1 g/dL (median 12.4 g/dL) at 6 months after HCT. All patients exhibited elevated resting CBF values prior to HCT (123.8 ± 32.2 mL blood/100 g tissue/min, median 112.8 mL blood/100 g tissue/min), that decreased following HCT (71.1 ± 32.1 mL blood/100 g tissue/min, median 72.8 mL blood/100 g tissue/min) (Table and Figure). None of the patients had any clinical neurological complications or imaging evidence of new infarcts or anatomical abnormalities in the follow up period.ConclusionOur preliminary results indicate that it is feasible to quantify CBF in patients with SCD before and after HCT using MRI. We demonstrate that cerebral hemodynamics improve after HCT in children with SCD, indicated by a decrease in CBF to near normal values (normal CBF ~80 mL blood/100 g tissue/min). The more substantial changes (-50% and -78%) are seen in children who were not receiving CTT, suggesting that CTT might partially mitigate CBF elevation prior to HCT. Nevertheless, 2 patients receiving CTT prior to HCT also had a further modest decrease in CBF after HCT (-5% and -18%). We plan to follow these changes at serial time points annually after HCT and correlate them with changes in neurocognitive functioning and other functional MRI measures. Improved CBF is expected to reduce stroke risk and may also preserve or improve neurocognitive functioning, and prospective monitoring of these outcomes are underway.Data on all the study participants who have undergone an HCT and had 2 serial MRIs performed by the ASH annual meeting will be presented. [Display omitted] DisclosuresSharma: Vertex Pharmaceuticals/CRISPR Therapeutics: Other: Salary support paid to institution; Medexus Inc: Consultancy; CRISPR Therapeutics: Other, Research Funding; Novartis: Other: Salary support paid to institution; Spotlight Therapeutics: Consultancy; Vindico Medical Education: Honoraria. Triplett: Miltenyi: Other: Travel, meeting registration. Hankins: Vindico Medical Education: Consultancy; UpToDate: Consultancy; Global Blood Therapeutics: Consultancy; Bluebird Bio: Consultancy.

Transfusional Iron Overload in Sickle Cell Patients:Outcomes of Chelation Therapy

Iron (Fe) overload is not rare among sickle cell disease (SCD) patients. It results from either chronic transfusions for primary or secondary stroke prevention, or more commonly sporadic, mostly unnecessary transfusions and are associated with significant morbidity, secondary to hepatic, cardiac and renal Fe deposition. Previous studies at our Center showed that 12% of the adult SCD population had Fe overload, and vast majority of these (80%) resulted from episodic transfusions (Son et al, 2013). Subsequent studies showed that the Fe regulatory peptide, hepcidin was appropriately upregulated in SCD subjects with Fe overload, and the plasma levels of the glycoprotein hormone erythroferrone (ERFE) was not as high as that found in patients with transfusion dependent beta thalassemia (TDT) due to the absence of significant ineffective erythropoiesis in SCD (Thawer et al, 2017, Mangaonkar et al, Brit. J. Haematol, 2020). We report on the utilization and outcomes in Fe overloaded SCD patients who were prescribed the oral chelating agent deferasirox.22 patients were prescribed deferasirox; median age was 38, 12 female 10 male. 21 had Hb SS, and 1 had s-b 0 thalassemia. Deferasirox dose ranged from 720-2500 mg/day (12 to 28 mg/Kg/day). Nonadherence was ascertained by patients' own admission. Figures 1-3 show the pre and post ferritin levels in subjects who were on deferasirox, and in controls; patients who took deferasirox had a more pronounced decrease in their ferritin (p=.004 vs p=.74). Although hepatic MRI for liver iron content (LIC) was not available on all patients, in those who underwent MRI there was a correlation between LIC and serum ferritin obtained at close temporal proximity (Fig. 4). Most common side effects of deferasirox were gastrointestinal (abdominal pain, nausea, vomiting, diarrhea), which were seen less commonly with the newer oral formulation (Jadenu).Several conclusions can be drawn from our observation on relatively small number of patients: 1) Deferasirox is effective in decreasing Fe overload as shown by serum ferritin levels 2) Second generation of oral deferasirox is better tolerated, and therefore is associated with improved adherence, 3) Documentation of a decrease in LIC with chelation will be important for the reversal of Fe induced organ damage, and 4) Parallel studies of the levels of Fe regulatory peptides hepcidin and erythroferrone (ERFE) will clarify the effect of chelation therapy on biomarkers of Fe metabolism. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Social Network-Based Digital Stroke Prevention: Opportunities, Results and Prospects

Aim. To study the possibilities and limitations of the social network as a digital medical tool, which is aimed at improving programs for primary and secondary stroke prevention in young people.Material and methods. The study was carried out in the format of online training for volunteers. At the first stage of the work, the online school “Stroke in Young People” was announced in 8 medical blogs. As part of the school, a special account was created for readers (n=1354). At the second stage, 49 respondents (4% of men, whose average age was 24.4±5.2 years) were selected from 1354 listeners, who were surveyed on “Awareness of risk factors and stroke symptoms among users of social networks” before and after the online school.Results. The online school audience is predominantly female (91%), and 43% of readers were in the 25-34 age group. The total number of people who listened to and read the online school material is 8712 people. 17% worked in the healthcare system, and 22% of respondents had a history of stroke. 38 (78%) people of the 2nd stage among the respondents independently searched for information about stroke earlier, and 30 (61%) received this information passively from medical workers in 2020. Before the online school start, the majority of respondents (over 60%) were aware of 2 out of 7 stroke risk factors (dyslipidemia and arterial hypertension) and 3 out of 6 stroke signs (drooping of the face half, weakness in the limbs and difficulty speaking). Less than 40% of the participants considered the stroke risk factors for diabetes mellitus, other cardiovascular diseases (CVD), obesity, and alcohol use; less than 20% were aware of stroke symptoms such as impaired vision and coordination and very severe headache. After completing online learning, the greatest increase in knowledge was found among the following risk factors – smoking and other CVDs (p&lt;0.05); stroke symptoms - headache and drooping of the face half (p&lt;0.05).Conclusion. The online school aroused interest among healthcare workers and people without medical education, including those with stroke. Most of the respondents believed that they knew how to prevent a stroke (over 80%) and would be able to provide first aid to a person with a stroke (over 90%). At the same time, the awareness of risk factors and stroke symptoms was low prior to the start of learning, even though the study included healthcare workers and stroke survivors. Online learning has led to increased awareness of some risk factors and stroke symptoms. Social media can be one of the tools for medical prevention of stroke in young people, but program planning should take into account the way the material is presented and its readability.

P.075 Incidence of Stroke Associated With Antithrombotic Agent Interruption

Background: Antithrombotic medications are used in the primary and secondary prevention of ischemic stroke. Previous studies have identified that up to 5.2% of ischemic strokes are associated with antithrombotic interruption, leading to significant mortality and healthcare burden. Our study aims to identify the prevalence of ischemic strokes presenting to a regional stroke centre associated with antithrombotic interruption, and to understand common reasons for medication interruption. Methods: A retrospective chart review was performed, which included 193 patients with ischemic stroke presenting to Greater Niagara General Hospital from January 2018-December 2019. Baseline demographics were recorded and patient medical records were reviewed for evidence of antithrombotic interruptions. Results: Table 1. Conclusions: Our cohort identified a significant proportion (8.3%) of ischemic strokes with documented antithrombotic interruption. Most common reasons for interruption were non-adherence and discontinuation due to previous adverse event. The results identify possible areas for improvement within patient education and safe re-initiation of antithrombotics following adverse events.

Association between Milk Intake and Incident Stroke among Japanese Community Dwellers: The Iwate-KENCO Study.

We aimed to evaluate the association between the milk consumption and incident stroke in a Japanese population, where milk consumption is lower than that of Western countries. In total, 14,121 participants (4253 men and 9868 women) aged 40–69 years, free from cardiovascular diseases (CVD) were prospectively followed for 10.7 years. Participants were categorized into four groups according to the milk intake frequency obtained from a brief-type self-administered diet questionnaire. The adjusted HRs of total stroke, ischemic stroke and haemorrhagic stroke associated with milk intake frequency were calculated using the Cox proportional hazards model. During the follow-up, 478 stroke cases were detected (208 men and 270 women). Compared to women with a milk intake of <2 cups/week, those with an intake of 7 to <12 cups/week had a significantly low risk of ischemic stroke in a model adjusting CVD risk factors; the HR (95% CI) was 0.53 (0.32–0.88). No significant associations were found in men. This study suggested that milk intake of 7 to <12 cups/week decreased the risk of ischemic stroke in Japanese women. Milk intake of about 1 to <2 cups/day may be effective in the primary prevention of ischemic stroke in a population with low milk intake.

Problems of selecting an anticoagulant for secondary stroke prevention in patients with atrial fibrillation

The article describes the urgent problem of ischemic stroke prevention in patients with atrial fibrillation. It is proved that ischemic stroke in combination with AF is the most severe in terms of developing stable motor and speech disorders and disability. The frail older patients, as well as patients with swallowing disorders and reduced medical adherence present a special problem from this point of view. The most famous clinical studies on secondary prevention of cardioembolic stroke are RE-LY, ROCKET-AF, and ARISTOTLE. Based on subanalyses of randomized controlled trials, direct oral anticoagulants demonstrated a favorable efficacy profile in patients with atrial fibrillation and stroke/ transient ischemic attack, but the level of knowledge on each of them remained different. A number of advantages of rivaroxaban for primary and secondary prevention of stroke in patients with atrial fibrillation, including the elderly and patients with cognitive impairments and swallowing disorders, have been demonstrated.

Left Atrial Appendage Closure for Primary and Secondary Stroke Prevention in Patients With Hypertrophic Cardiomyopathy and Atrial Fibrillation: A Pilot Study.

Background: The aim of this study was to investigate the efficacy of left atrial appendage closure (LAAC) for primary and secondary stroke prevention in patients with hypertrophic cardiomyopathy (HCM) and atrial fibrillation (AF).Methods: This pilot study enrolled 36 patients with HCM and AF who underwent LAAC between April 2017 and December 2019, of whom 22 were for primary stroke prevention and 14 were for secondary prevention.Results: The patients enrolled in this study had non-obstructive (86.1%) or mild obstructive (13.9%) HCM. Patients in the Secondary Prevention Group had higher CHA2DS2-VASc scores (5.1 ± 1.4 vs. 2.6 ± 1.6, P < 0.001) and higher HAS-BLED scores (2.8 ± 1.0 vs. 1.5 ± 0.9, P < 0.001) compared with those in the Primary Prevention Group. Successful closure with satisfactory seals (residual leak ≤ 5 mm) was achieved in all patients, with complete occlusion in 86.4% of the Primary Prevention Group and 92.9% of the Secondary Prevention Group. Procedural-related complications included one pericardial effusion and one groin hematoma. One device-related thrombus was identified in the Secondary Prevention Group and resolved after anticoagulation. During a mean follow-up time of 28.4 months, one bleeding event was recorded. There were no thromboembolic events or deaths in either group, with 97.2% of the patients achieving freedom from anticoagulation therapy.Conclusions: Initial results suggest that LAAC can be a safe and feasible alternative for primary and secondary stroke prevention in selected patients with HCM and AF. Further studies with larger samples are required.

Predicting stroke risk in Chinese hypertensive population using machine learning

Abstract Background Stroke is the leading cause of death in China, and the stroke burden is especially high in rural areas. Risk prediction is essential for primary prevention of stroke. However, uncertainty remains about the optimal methodology for analyzing stroke risk. In this study, we aim to determine the most effective stroke prediction method in a targeted population and establish a general framework and pipeline for future analysis. Purpose 1) to determine the most effective stroke prediction method in a targeted population and 2) to establish a general framework and pipeline for future analysis. Methods Data were obtained from the China Stroke Primary Prevention Trial (CSPPT), a randomized, double-blind, multi-center clinical trial. 20,702 hypertensive patients without prior history of stroke were included in the study. The primary outcome was new nonfatal and fatal stroke (ischemic or hemorrhagic) occurring between baseline and follow-up (a median of 4.2 years). All suspected stroke cases were collected and further validated by the event adjudication committee. We compared two regression models (logistic regression and step wise logistic regression) and two machine learning methods (extreme gradient boosting and random forest). All models were trained using questionnaire data with and without laboratory data, then analyzed and compared. The primary outcome was defined as first stroke. Accuracy, sensitivity, specificity and AUCs (area under receiver operating characteristic curve) were used to assess each model. AUCs were used to evaluate the performance of each analysis method. Results In our data set with 20,702 samples and 127 variables, the highest AUCs (0.775 (0.725–0.826)) were observed with RUS (random under sampling) applied to RF (random forest). Before applying data balancing techniques, all analysis methods showed very low sensitivity (around 0.01), very high accuracy (around 0.97), and very high specificity (around 1.00). The mean AUCs were 0.741 (0.678–0.803). After data balancing techniques were applied, we observed an increase in sensitivity and decreases in accuracy and specificity. Different data balancing techniques had different effects on analysis methods. No significant effect on AUCs was observed; the range of increase and decrease was around 0.01. Similar overall patterns were observed when training with laboratory test data added. The mean AUCs were 0.739 (0.679–0.799) and 0.734 (0.674–9.795) for all models using data with and without laboratory test respectively. The 10 most important variables as determined by the model were selected as stroke risk predictors for all analysis models. Conclusion The most effective stroke prediction method in this Chinese rural hypertensive population is RUS applied to RF. The optimal analysis method and variable selection depends on data-specific features. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Key R&amp;D Projects, Jiangxi [20203BBGL73173] National Key Research and Development Program [2016YFE0205400]

Carotid sinus syndrome in carotid angioplasty with stenting

Introduction. Significant progress has been made in primary stroke prevention, including through the widespread use of carotid angioplasty with stenting (CAS). At the same time, there is a growing number of publications reporting the development of carotid sinus syndrome (CSS) (haemodynamic instability) in the periope- rative period, as well as cerebral and cardiac complications and death, which requires in-depth study to improve the quality of medical care for patients with carotid artery stenosis.&#x0D; The aim of the study was to determine the frequency, risk factors, clinical features and outcomes of CSS in patients with carotid artery stenosis undergoing CAS.&#x0D; Materials and methods. The study included 120 patients with carotid artery disease, who underwent an elective surgical intervention consisting of transluminal balloon angioplasty. All patients underwent comprehensive clinical and laboratory tests and imaging studies.&#x0D; Results. CSS developed in 70% of cases (n = 84) of carotid artery stenosis, and was significantly more common in men than women (71.4% vs. 28.6%, respectively) (p 0.05). The median age of all patients with CSS was 68 (4491) years. Mixed form of CSS was significantly more common than the cardioinhibitory or vasodepressor forms (p 0.05). In more than half of all cases, symptoms developed during balloon dilatation or within an hour afterwards. The duration of CSS was 3040 hours. Contralateral carotid occlusion was detected in 12 (10%) patients, significantly (p 0.05) more often in patients with CSS (13%) compared to patients without CSS (2.8%).&#x0D; Conclusion. Regardless of stenosis severity or symptoms, CAS is accompanied by CSS in 2/3 of cases. The CSS is predominantly a mixed type and can be accompanied by loss of consciousness in rare cases. CSS appears both intraoperatively and in the early postoperative period, and its average duration is 1.5 days. A factor that may be associated with CSS development is contralateral carotid artery occlusion (p 0.05).

Sleep and cerebrovascular disease

SLEEP and CEREBROVASCULAR DISEASE Review of the current knowledge base concerning the complex interaction between sleep, sleep disorders and cerebrovascular disease. Through reviewing the literature, recommendations will be provided concerning primary and secondary prevention of stroke through addressing the diagnosis and treatment of sleep-related conditions.

Perspectives of mobile technologies

Reducing stroke risk behaviors is associated with reduced stroke incidence. The free Stroke Riskometer™ mobile phone App (“App”) developed by AUT University (New Zealand) is a novel tool for primary stroke prevention. The App is being used in 78 countries and translated into 19 languages covering 70% of the world population (5.3 billion people).

Associations of Medicaid Expansion With Access to Care, Severity, and Outcomes for Acute Ischemic Stroke.

Multiple states have not expanded Medicaid under the Affordable Care Act, resulting in higher uninsured rates in states with high stroke burdens. This study aimed to evaluate the association of Medicaid expansion with changes in health insurance coverage, severity of presentation, access to care, and outcomes among patients with acute ischemic stroke. A retrospective, difference-in-differences analysis of Get With The Guidelines-Stroke registry data. The study population comprised first-time ischemic stroke admissions from 2012 to 2018 for patients aged 19 to 64 in 45 states (27 that expanded Medicaid and 18 that did not). A probable low-income cohort was defined based on having Medicaid, no insurance/self-pay, or undocumented insurance. Outcomes analyzed were indicators of health insurance status, stroke severity, use of emergency services, time to acute care, in-hospital mortality, receipt of rehabilitation, discharge disposition, and level of disability. In the starting population (N=342 765), Medicaid-covered stroke admissions rose from 12.2% to 18.1% in expansion states and from 10.0% to only 10.6% in nonexpansion states, while uninsured admissions declined from 15.0% to 6.7% in expansion states and from 24.0% to 19.2% in nonexpansion states. In the low-income cohort (N=95 086; 28% of starting population), Medicaid expansion was associated with increased odds of discharge to a skilled nursing facility (adjusted odds ratio, 1.33 [95% CI, 1.12-1.59]) and transfer to any rehabilitation facility among those eligible (adjusted odds ratio, 1.24 [95% CI, 1.08-1.41]) and lower odds of discharge home (adjusted odds ratio, 0.89 [95% CI, 0.80-0.98]). Expansion was not associated with any other outcomes. Medicaid expansion is associated with fewer uninsured hospitalizations for acute ischemic stroke and increased rehabilitation at skilled nursing facilities. More targeted interventions may be needed to improve other stroke outcomes in the low-income US population. Future research should evaluate the impact of health care reform on primary stroke prevention.

Identification of Good Practices in Long-Term Exercise-Based Rehabilitation Programs in Stroke Patients.

Physical activity is an important factor for primary and secondary stroke prevention. The process of stroke rehabilitation includes early and late physical activity and exercise, which prevents further stoke and improve patients' quality of life. MY WAY project, an ERASMUS+ SPORT program, is aimed at analyzing and developing or transferring best innovative practices related to physical activity and exercise enhancing health in poststroke patients. The aim of the study was to identify, analyze, and present the good practices and strategies to encourage participation in sport and physical activity and engage and motivate chronic stroke patients to perform physical activity changing their lifestyle and to maintain a high adherence to long-term exercise-based rehabilitation programs. Our results demonstrated that unified European stroke long-term exercise-based rehabilitation guidelines do not exist. It seems that low training frequency with high aerobic exercise intensity may be optimal for improved physical performance and quality of life in combination with a high adherence. It is important to optimize the training protocols suitable for each patient. The continuous education and training of the specialized professionals in this field and the presence of adequate structures and cooperation between different healthcare centers are important contributors. The clear objective for each country should be to systematically make the necessary steps to enhance overall exercise-based stroke rehabilitation attendance in the long term. Long-term interventions to support the importance of physical exercise and lifelong exercise-based rehabilitation in chronic stroke patients should be created, what coincides with the goal of the MY WAY project.

Role of diabetes in stroke: Recent advances in pathophysiology and clinical management

The increasing prevalence of diabetes and stroke is a major global public health concern. Specifically, acute stroke patients, with pre-existing diabetes, pose a clinical challenge. It is established that diabetes is associated with a worse prognosis after acute stroke and the various biological factors that mediate poor recovery profiles in diabetic patients is unknown. The level of association and impact of diabetes, in the setting of reperfusion therapy, is yet to be determined. This article presents a comprehensive overview of the current knowledge of the role of diabetes in stroke, therapeutic strategies for primary and secondary prevention of cardiovascular disease and/or stroke in diabetes, and various therapeutic considerations that may apply during pre-stroke, acute, sub-acute and post-stroke stages. The early diagnosis of diabetes as a comorbidity for stroke, as well as tailored post-stroke management of diabetes, is pivotal to our efforts to limit the burden. Increasing awareness and involvement of neurologists in the management of diabetes and other cardiovascular risk factors is desirable towards improving stroke prevention and efficacy of reperfusion therapy in acute stroke patients with diabetes.

Capacity Building for Primary Stroke Prevention Teams in Children Living With Sickle Cell Anemia in Africa

BackgroundNigeria has the highest proportion of children with sickle cell anemia (SCA) globally; an estimated 150,000 infants with SCA are born annually. Primary stroke prevention in children with SCA must include Nigeria. We describe capacity-building strategies in conjunction with two National Institutes of Health–funded primary stroke prevention trials (a feasibility trial and phase III randomized controlled trial) with initial hydroxyurea treatment for children with SCA and abnormal transcranial Doppler (TCD) velocities in Nigeria. We anticipated challenges to conducting clinical trials in a low-resource setting with a local team that had not previously been involved in clinical research and sought a sustainable strategy for primary stroke prevention. MethodsThis is a descriptive, prospective study of challenges, solutions, and research teams in two trials that enrolled a total of 679 children with SCA. ResultsAs part of the capacity-building component of the trials, over eight years, 23 research personnel (physicians, nurses, research coordinators, a statistician, and a pharmacist) completed a one-month research governance and ethics training program at Vanderbilt University Medical Center, USA. A lead research coordinator for each site completed the Society of Clinical Research Professionals certification. TCD machines were donated; radiologists and nonradiologists were trained and certified to perform TCD. A scalable E-prescription was implemented to track hydroxyurea treatment. We worked with regional government officials to support ongoing TCD-based screening and funding for hydroxyurea for children with SCA at a high risk of stroke. ConclusionsOur trials and capacity building demonstrate a sustainable strategy to initiate and maintain pediatric SCA primary stroke prevention programs in Africa.

Timed Average Mean Maximum Velocity (TAMMV) of Cerebral Blood Flow of Children and Adolescents with Sickle cell Disease: correlation with clinical and hematological profiles in country.

Detection of abnormal TAMMV with transcranial Doppler is fundamental in primary stroke prevention in children with sickle cell disease (SCD). The study aimed at evaluating TAMMV and correlating it with clinical and hematological profiles of children and adolescent with SCD. Transcranial Doppler was performed on subjects aged 2-16 years, using a 2 MHz probe placed over the transtemporal windows. Pulse oximetry was used to determine the peripheral oxygen saturation while clinical and hematological profiles were retrieved from their medical records. One hundred and thirty five patients were recruited. The mean TAMMV was 125cm/s. Patients with HbSS had a significantly higher TAMMV (131cm/s) than those with HbSC (107cm/s). Only one (0.74%) patient had abnormal TAMMV. TAMMV correlated inversely with oxygen saturation, Hct and patient's age, and positively with white cell and platelet counts. Previous history of acute chest syndrome (ACS) and recurrent painful crises increased the risk of development of abnormal and conditional velocity. Frequency of abnormal TAMMV in this study was low. Younger children and those with HbSS had higher TAMMV. Age, oxygen saturation and haematocrit correlated negatively while white cell and platelet counts correlated positively with TAMMV. Previous history of ACS and recurrent bone pain were associated with increased risk of having abnormal and conditional TAMMV.

BETWEEN THE DEVIL AND DEEP BLUE SEA - ANTICOAGULATION IN CARDIOEMBOILC STROKE

Stroke is the commonest cause of mortality and morbidity after coronary artery disease. According in India stroke factsheet updated in 2021, the estimated age-adjusted prevalence rate for stroke ranges between 84-262/100,000 in rural and 334-424/100,000 in urban areas. Ischemic stroke is the commonest followed by cardioembolic which is 20% which may be higher in developing countries because of illiteracy and lower socioeconomic status. Cardioembolic strokes are usually severe in presentation and prone for early recurrence. The risk of long term recurrence and mortality are also high. Hemorrhagic transformation occurs in up to 71% of cardioembolic strokes. Atrium, ventricle and valves are the high-risk origins. This article highlights the importance of balancing between thromboembolism and bleeding risks while making therapeutic decisions. Anticoagulation is indicated both for primary and secondary stroke prevention. The role of Novel oral anticoagulant versus warfarin and they edge over as they don't need INR monitoring .Thrombogenic atrial substrate even in the absence of atrial brillation can predispose to atrial thromboembolism.TEE allows better visualization (aortic atheromas, patent foramen ovale, atrial septal aneurysms) of earlier crytogenic lesions elucidating a cause and thereby reducing the embolic risk. Because of varied etiology and presentation, a tailored individual approach is needed

Quality of stroke guidelines in low- and middle-income countries: a systematic review.

ObjectiveTo identify gaps in national stroke guidelines that could be bridged to enhance the quality of stroke care services in low- and middle-income countries.MethodsWe systematically searched medical databases and websites of medical societies and contacted international organizations. Country-specific guidelines on care and control of stroke in any language published from 2010 to 2020 were eligible for inclusion. We reviewed each included guideline for coverage of four key components of stroke services (surveillance, prevention, acute care and rehabilitation). We also assessed compliance with the eight Institute of Medicine standards for clinical practice guidelines, the ease of implementation of guidelines and plans for dissemination to target audiences.FindingsWe reviewed 108 eligible guidelines from 47 countries, including four low-income, 24 middle-income and 19 high-income countries. Globally, fewer of the guidelines covered primary stroke prevention compared with other components of care, with none recommending surveillance. Guidelines on stroke in low- and middle-income countries fell short of the required standards for guideline development; breadth of target audience; coverage of the four components of stroke services; and adaptation to socioeconomic context. Fewer low- and middle-income country guidelines demonstrated transparency than those from high-income countries. Less than a quarter of guidelines encompassed detailed implementation plans and socioeconomic considerations.ConclusionGuidelines on stroke in low- and middle-income countries need to be developed in conjunction with a wider category of health-care providers and stakeholders, with a full spectrum of translatable, context-appropriate interventions.