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Background and Purpose There are reports of decline in the rates of acute emergency presentations during coronavirus disease 2019 (COVID-19) pandemic including stroke. We performed a meta-analysis of the impact of COVID-19 pandemic on rates of stroke presentations and on rates of reperfusion therapy. Methods Following the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines, we systematically searched the literature for studies reporting changes in stroke presentations and treatment rates before and during the COVID-19 pandemic. Aggregated data were pooled using meta-analysis with random-effect models. Results We identified 37 observational studies (n=375,657). Pooled analysis showed decline in rates of all strokes (26.0%; 95% confidence interval [CI], 22.4 to 29.7) and its subtypes; ischemic (25.3%; 95% CI, 21.0 to 30.0), hemorrhagic (27.6%; 95% CI, 20.4 to 35.5), transient ischemic attacks (41.9%; 95% CI, 34.8 to 49.3), and stroke mimics (45.6%; 95% CI, 33.5 to 58.0) during months of pandemic compared with the pre-pandemic period. The decline was most evident for mild symptoms (40% mild vs. 25%–29% moderate/severe). Although rates of intravenous thrombolytic (IVT) and endovascular thrombectomy (EVT) decreased during pandemic, the likelihood of being treated with IVT and EVT did not differ between the two periods, both in primary and in comprehensive stroke centers (odds ratio [OR], 1.08; 95% CI, 0.94 to 1.24 and OR, 0.95; 95% CI, 0.83 to 1.09, respectively). Conclusions Rates of all strokes types decreased significantly during pandemic. It is of paramount importance that general population should be educated to seek medical care immediately for stroke-like symptoms during COVID-19 pandemic. Whether delay in initiation of secondary prevention would affect eventual stroke outcomes in the long run needs further study.

Embolic stroke of unknown source (ESUS) represents one in five ischemic strokes. Ipsilateral non-stenotic carotid plaques are identified in 40% of all ESUS. In this narrative review, we summarize the evidence supporting the potential causal relationship between ESUS and non-stenotic carotid plaques; discuss the remaining challenges in establishing the causal link between non-stenotic plaques and ESUS and describe biomarkers of potential interest for future research. In support of the causal relationship between ESUS and non-stenotic carotid plaques, studies have shown that plaques with high-risk features are five times more prevalent in the ipsilateral vs. the contralateral carotid and there is a lower incidence of atrial fibrillation during follow-up in patients with ipsilateral non-stenotic carotid plaques. However, non-stenotic carotid plaques with or without high-risk features often coexist with other potential etiologies of stroke, notably atrial fibrillation (8.5%), intracranial atherosclerosis (8.4%), patent foramen ovale (5–9%), and atrial cardiopathy (2.4%). Such puzzling clinical associations make it challenging to confirm the causal link between non-stenotic plaques and ESUS. There are several ongoing studies exploring whether select protein and RNA biomarkers of plaque progression or vulnerability could facilitate the reclassification of some ESUS as large vessel strokes or help to optimize secondary prevention strategies.

Objective: To summarize data on atrial fibrillation (AF) detection rates and predictors across different rhythm monitoring strategies in patients with cryptogenic stroke (CS) or embolic stroke of undetermined source (ESUS). Methods: MEDLINE, Embase, and Web of Science were searched to identify all published studies providing relevant data through July 6, 2020. Random-effects meta-analysis method was used to pool estimates. Results: We included 47 studies reporting on a pooled population of 8,215 patients with CS or ESUS. Using implantable cardiac monitor (ICM), the pooled rate of AF was 12.2% (95% CI 9.4–15.0) at 3 months, 16.0% (95% CI 13.2–18.8) at 6 months, 18.7% (95% CI 15.7–21.7) at 12 months, 22.8% (95% CI 19.1–26.5) at 24 months, and 28.5% (95% CI 17.6–39.3) at 36 months. AF rates were significantly higher in patients with ESUS vs CS (22.0% vs 14.2%; p

Hemorrhagic transformation (HT) is a common complication in patients with acute ischemic stroke. It occurs when peripheral blood extravasates across a disrupted blood brain barrier (BBB) into the brain following ischemic stroke. Preventing HT is important as it worsens stroke outcome and increases mortality. Factors associated with increased risk of HT include stroke severity, reperfusion therapy (thrombolysis and thrombectomy), hypertension, hyperglycemia, and age. Inflammation and the immune system are important contributors to BBB disruption and HT and are associated with many of the risk factors for HT. In this review, we present the relationship of inflammation and immune activation to HT in the context of reperfusion therapy, hypertension, hyperglycemia, and age. Differences in inflammatory pathways relating to HT are discussed. The role of inflammation to stratify the risk of HT and therapies targeting the immune system to reduce the risk of HT are presented.

INTRODUCTION: although the main manifestations of COVID-19 are respiratory, several neurological symptoms and complications have also been reported. The pandemic seems to have some epidemiological specificities in sub-Saharan Africa, and this may be reflected in the type and frequency of neurological symptoms. This study aimed to report neurological manifestations associated with symptomatic COVID-19 in a sub-Saharan African setting. METHODS: we conducted a retrospective review of symptomatic PCR-confirmed COVID-19 cases admitted to the Bafoussam Regional Hospital between March and September 2020. Patients’ files were reviewed at discharge by a consultant neurologist. Socio-demographic characteristics, co-morbidities, symptoms on admission, neurological symptoms during hospitalization, management, and in-hospital outcome were recorded. Comparisons between patients with and without neurological symptoms were performed using Fisher’s exact and Mann-Whitney U test. RESULTS: we enrolled 177 symptomatic patients (68% men). Mean age was 54.6 ± 17.8 years (range 2-99 years). Co-morbidities were present in 57.6% of patients, including hypertension (27.1%) and diabetes mellitus (25.4%). Neurological symptoms were found in 113 (63.8%) patients. The most frequent were headache (39.0%), myalgia (35.6%), anosmia (11.9%), impaired consciousness (10.7%) and delirium (5.6%). Regarding the presenting symptoms, fever was more frequent in patients with neurological symptoms than in those without (81.4% versus 50.0%, p= 0.001), while digestive symptoms were less frequent in patients with neurological symptoms (0.9% versus 9.4%, p= 0.004). CONCLUSION: neurological manifestations are frequent and heterogeneous in patients with symptomatic COVID-19. Further studies are needed to clarify the pathophysiology of neurological symptoms in COVID-19 and their impact on patients’ long-term outcome.

Background and purpose Detection of atrial fibrillation (AF) after acute ischaemic stroke is pivotal for the timely initiation of anticoagulation to prevent recurrence. Besides heart rhythm monitoring, various blood biomarkers have been suggested as complimentary diagnostic tools for AF. We aimed to summarise data on the performance of cardiac natriuretic peptides for the diagnosis of covert AF after acute ischaemic stroke and to assess their potential clinical utility.Methods We searched PubMed and Embase for prospective studies reporting the performance of B-type natriuretic peptide (BNP) or N-terminal pro-BNP (NT-proBNP) for the diagnosis of covert AF after acute ischaemic stroke. Summary diagnostic performance measures were pooled using bivariate meta-analysis with a random-effect model.Results We included six studies focusing on BNP (n=1930) and three studies focusing on NT-proBNP (n=623). BNP had a sensitivity of 0.83 (95% CI 0.64 to 0.93), a specificity of 0.74 (0.67 to 0.81), a positive likelihood ratio of 3.2 (2.6 to 4.0) and a negative likelihood ratio of 0.23 (0.11 to 0.49). NT-proBNP had a sensitivity of 0.91 (0.65 to 0.98), a specificity of 0.77 (0.52 to 0.91), a positive likelihood ratio of 3.9 (1.8 to 8.7) and a negative likelihood ratio of 0.12 (0.03 to 0.48). Considering a pretest probability of 20%, BNP and NT-proBNP had post-test probabilities of 45% and 50%.Conclusions NT-proBNP has a better performance than BNP for the diagnosis of covert AF after acute ischaemic stroke. Both biomarkers have low post-test probabilities and may not be used as a stand-alone decision-making tool for the diagnosis of covert AF in patients with acute ischaemic stroke. However, they may be useful for a screening strategy aiming to select patients for long-term monitoring of the heart rhythm.

Background and objective: In sub-Saharan Africa, data on prevalence, risk factors and pathobiology of carotid atherosclerosis are scarce. We aimed to investigate the relationship between biomarkers of endothelial dysfunction and carotid atherosclerosis. Methods: Carotid ultrasound was performed in 66 patients. Plasma concentration of ICAM-1, PAI-1, VEGF, and soluble thrombomodulin were measured by ELISA. A univariable logistic regression analysis was performed to study the relationship between carotid atherosclerosis, biomarkers of endothelial dysfunction, and various demographic and clinical parameters of the participants. Results: The mean age of the participants was 58.7 years (95% CI: 54.4–63.1). Carotid atherosclerosis was diagnosed in 39.4% (95% CI: 27.6–52.2). In the univariable logistic regression, the following factors were associated with carotid atherosclerosis: age > 45 years (OR = 12.0, 95% CI: 1.4–98.8, p = .02), hypertension (OR = 3.8, 95% CI: 1.2–12.1, p = .02), and high-level of soluble thrombomodulin (OR = 3.4, 95% CI: 1.2–10.0, p = .02). Conclusions: There is an association between high levels of soluble thrombomodulin and carotid atherosclerosis in Malawian adults. Further studies with a larger sample size are needed to confirm our findings in other African populations.

BackgroundIn sub-Saharan Africa, there is a dearth of epidemiologic data on the burden of cerebral atherosclerosis. This is explained by the limited availability and the high cost of standard vascular imaging techniques. Neurovascular ultrasound is portable, cheaper and non-invasive and could, therefore, represent a reasonable alternative to fill this knowledge gap. We explored the feasibility of neurovascular ultrasound in Malawian adults with acute stroke-like syndrome to inform the design of future large stroke studies comparing its diagnostic performance to that of gold standard vascular imaging techniques in sub-Saharan Africa.MethodsWe enrolled consecutive patients diagnosed with acute stroke-like syndrome based on the World Health Organization definition. Clinical and demographic data were recorded, and a comprehensive neurovascular ultrasound was performed. Fisher's exact and Kruskal-Wallis tests were used to study the relationship between atherosclerosis and potential risk factors.ResultsSixty-six patients were enrolled (mean age: 58.7 years). The frequency of extracranial atherosclerosis was 39.4% (n = 26, 95% CI: 28.6-52.2). There were 12 patients with abnormal carotid intima media thickness (18.2%, 95% CI: 9.8-29.6) and 14 patients with a carotid plaque (21.2%, 95% CI: 12.1-33.0). The frequency of intracranial atherosclerosis was 19.2% (95%CI: 6.6-39.4) in 26 patients with successful transcranial insonation. Hypertension (80.8 versus 52.5%, p = 0.03) and hypercholesterolemia (11.5 versus 0.0%, p = 0.05) were more prevalent in patients with extracranial atherosclerosis.ConclusionsThis study demonstrates the feasibility of neurovascular ultrasound to assess cervical arteries in adults with stroke-like syndrome in sub-Saharan Africa. There is a high rate of transcranial insonation failure in this setting, highlighting the need for echocontrast agents.

Background: Soil-transmitted helminthiases (STHs) are among the most prevalent afflictions of the developing world, with approximately 2 billion people infected worldwide. Heavily infected individuals suffer from severe morbidity that can result in death. These parasitic diseases also impair physical and mental growth in childhood, thwart educational advancement, and hinder economic development. Periodic deworming with Albendazole or Mebendazole of high-risk groups (school-age children, preschool children, and pregnant women) can significantly lower the levels of infections below the threshold associated with morbidity. However, an important proportion of the population (adults) is excluded from this high-risk group treatment based-strategy, and might lead to the persistence of these diseases in endemic areas despite the repeated treatments. The main objective of this study was to evaluate the contribution of this neglected at-risk group in the spread and persistence of STH in Cameroon. Methods: A cross sectional survey was conducted in the Akonolinga health district (Centre Region, Cameroon) to assess the prevalence and intensity of these helminth infections. Stool samples were collected from males and females, aged 18 years and over, and analyzed using the Kato-Katz technique. Results: A total of 334 patients, among which 181 (54.2%) females and 153 (45.8%) males, were examined. The STH of major concern was found in this group of individuals, with overall prevalence equal to 18.0% (95% CI: 14.2–22.4) for Ascaris lumbricoides, 43.7% (95% CI: 38.5–49.1) for Trichuris trichiura, and 7.5% (95% CI: 5.1–10.8) for Necator americanus. Conclusion: This study reveals that STH infections are prevalent in adults in the Akonolinga health district, with moderate to high risk and light intensity of infection. These infected adults might constitute a potential parasite reservoir and a source of dissemination and persistence of these infections, highlighting the need to really take into account this neglected group of individuals in the mass treatment policy.

BackgroundStudies in high-income settings have shown association between Cytomegalovirus (CMV) infection and adverse cardiovascular outcome, especially in HIV infection. We aimed to study the association between serum concentration of anti-CMV IgG and ischaemic stroke in HIV-infected Malawians.MethodsOur sample was derived from a case-control stroke study in Malawi. Serum concentration of anti-CMV IgG was measured using enzyme-linked immunosorbent assay. Multivariable logistic regression was used to study the association between high concentrations of anti-CMV IgG (above the third tertile) and ischaemic stroke while adjusting for cardiovascular risk factors.ResultsOverall, 139 HIV-positive adults (48.2% women; 48 ischaemic stroke cases and 91 controls; median age: 45 years) were included. The median CD4+ count was 136 and 401 cell/mm3 (IQR: [75-278] and [230-533]) in cases and controls, respectively. High concentration of anti-CMV IgG was associated with ischaemic stroke in the univariable model (OR = 2.56 [1.23-5.34]) but not after adjusting for duration of antiretroviral therapy (ART), CD4+ count, and other cardiovascular risk factors (OR = 0.94 [0.29-3.08]). Low CD4+ count was an independent predictor of stroke. There was a negative correlation between serum concentration of anti-CMV IgG and CD4+ count (rho = -0.30, p < 0.001).ConclusionsHigh concentration of anti-CMV IgG is not independently associated with ischaemic stroke in HIV-infected Malawians. Larger cohort studies are needed to further investigate the role of humoral response to CMV in the pathophysiology of HIV-associated stroke.

Introduction In Sub-Saharan Africa, the rising rates of cerebrovascular and cardiovascular diseases (CBD/CVD) are intersecting with an ageing HIV-infected population. The widespread use of antiretroviral therapy (ART) may confer an additive risk and may not completely suppress the risk associated with HIV infection. High-quality prospective studies are needed to determine if HIV-infected patients in Africa are at increased risk of CBD/CVD and to identify factors associated with this risk. This study will test the hypothesis that immune activation and dysfunction, driven by HIV and reactivation of latent herpesvirus infections, lead to increased CBD/CVD risk in Malawian adults aged ≥35 years.Methods and analysis We will conduct a single-centre, 36-month, prospective cohort study in 800 HIV-infected patients initiating ART and 190 HIV-uninfected controls in Blantyre, Malawi. Patients and controls will be recruited from government ART clinics and the community, respectively, and will be frequency-matched by 5-year age band and sex. At baseline and follow-up visits, we will measure carotid intima-media thickness and pulse wave velocity as surrogate markers of vasculopathy, and will be used to estimate CBD/CVD risk. Our primary exposures of interest are cytomegalovirus and varicella zoster reactivation, changes in HIV plasma viral load, and markers of systemic inflammation and endothelial function. Multivariable regression models will be developed to assess the study’s primary hypothesis. The occurrence of clinical CBD/CVD will be assessed as secondary study endpoints.Ethics and dissemination The University of Malawi College of Medicine and Liverpool School of Tropical Medicine research ethics committees approved this work. Our goal is to understand the pathogenesis of CBD/CVD among HIV cohorts on ART, in Sub-Saharan Africa, and provide data to inform future interventional clinical trials. This study runs between May 2017 and August 2020. Results of the main trial will be submitted for publication in a peer-reviewed journal.Trial registration number ISRCTN42862937.