Neurological complications of sickle cell disease in Africa: protocol for a systematic review

INTRODUCTION: Sickle cell disease (SCD) is highly prevalent in Africa. Considered as a public health problem, it is associated with high morbidity and mortality. Neurological complications of SCD can cause significant disability with important socioeconomic and psychological impact on the patients and their families, and can even lead to death if not properly managed. There are important knowledge gaps regarding the burden of neurological complications of SCD in African populations. We propose to conduct the first systematic review to summarise the epidemiological data available on neurological complications of SCD in Africa. METHODS AND ANALYSIS: We will search PubMed, MEDLINE, EMBASE and the African Index Medicus from 1 January 1950 to 31 May 2016 for studies of neurological complications of SCD in Africa. After study selection, full-text paper acquisition, data extraction and synthesis, we will assess all studies for quality, risk of bias and heterogeneity. Appropriate methods of meta-analysis will be used to pool prevalence estimates from studies with similar features, globally and in major subgroups. This protocol complies with the 2015 Preferred Reporting Items for Systematic reviews and Meta-Analysis protocols (PRISMA-P) guidelines. ETHICS AND DISSEMINATION: The proposed study will use published data. Therefore, there is no requirement for ethical approval. This review is expected to provide relevant data to help quantify the burden of neurological complications of SCD in African populations, inform policymakers and identify further research topics. The final report of the systematic review will be published in a peer-reviewed journal and presented at conferences. REVIEW REGISTRATION NUMBER: CRD42016039574

Endothelial dysfunction and carotid atherosclerosis in Malawian adults: A cross-sectional study

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

The significant gap between international standards and stroke management practices at Queen Elizabeth Central Hospital (Malawi): An audit report

Background The Queen Elizabeth Central Hospital (QECH) is preparing to set up the first stroke unit in Blantyre, Malawi. We conducted this audit to assess current stroke management practices and outcomes at QECH and identify priority areas for intervention. Methods From April to June 2018, we prospectively enrolled patients with acute stroke and collected data on clinical presentation, cardiovascular risk factors, investigations and interventions, in-hospital outcomes, and follow-up plans after discharge. The American Heart Association/American Stroke Association (AHA/ASA) guidelines were used as the standard of care for comparison. Results Fifty patients with acute stroke were enrolled (46% women, 54% men). The mean age was 63.1 years (95% CI: 59.7-66.6). The diagnosis of stroke was based on the World Health Organization criteria. The diagnosis was made within 24 hours of admission in 19 patients (38%). Acute revascularisation therapy was not available. Forty-eight patients (96%) had their vital signs checked at baseline and 140/90 mmHg in 34 patients (68%), including 4 with values >220/120 mmHg. Nine patients had an RBS >10 mmol/L and four received insulin. Prophylaxis for deep venous thrombosis was offered to 12 patients (24%). Aspiration pneumonia was reported in 16 patients (32%) and was the most common hospital complication. The mean duration of hospitalisation was 10.4 days (95% CI: 5.6-15.2), and case fatality was 18%. The modified Rankin scale at discharge was ≤2 in 32% of patients. Only four patients (8%) were transferred to a rehabilitation centre. At the time of discharge, only 32% of patients received education on stroke. Conclusion Acute stroke care is less than optimal in this setting. Simple interventions such as reducing the delay in making a stroke diagnosis, early swallow assessments, and closer monitoring of vital signs could make a significant difference in stroke outcome. Furthermore, treating cardiovascular risk factors and setting up health education programmes to improve secondary prevention represent key priorities

An exploratory cohort study of sensory extinction in acute stroke: prevalence, risk factors, and time course

Most studies on sensory extinction have focused on selected patients with subacute and chronic right hemisphere lesions. In studies conducted on acute stroke patients, risk factors and time course were not evaluated. Our aim was to determine the prevalence, risk factors, and time course of sensory extinction in the acute stroke setting. Consecutive patients with acute stroke were tested for tactile, visual, auditory, and auditory-tactile cross-modal extinction, as well as for peripersonal visuospatial neglect (PVN). Tests were repeated at 2, 7, 15, 30, and 90 days after initial examination. A multivariable logistic regression analysis was performed to test the association between sensory extinction and demographic and clinical risk factors. Seventy-three patients (38.4% women) were recruited: 64 with ischemic stroke and nine with haemorrhagic stroke. Mean age was 62.3 years (95% CI 58.8-65.7), mean NIHSS score was 1.6 (95% CI 1.2-2.1), and mean time to first examination was 4.1 days (95% CI 3.5-4.8). The overall prevalence of all subtypes of sensory extinction was 13.7% (95% CI 6.8-23.8). Tactile extinction was the most frequent subtype with a prevalence of 8.2% (95% CI 3.1-17.0). No extinction was found beyond 15 days after the first examination. After adjustment for age, sex, lesion side, type of stroke, time to first examination and stroke severity, a lesion volume ≥2 mL (adjusted OR = 38.88, p = 0.04), and presence of PVN (adjusted OR = 24.27, p = 0.04) were independent predictors of sensory extinction. The insula, the putamen, and the pallidum were the brain regions most frequently involved in patients with sensory extinction. Extinction is a rare and transient phenomenon in patients with minor stroke. The presence of PVN and lesion volume ≥2 mL are independent predictors of sensory extinction in acute stroke

A cross-sectional feasibility study of neurovascular ultrasound in Malawian adults with acute stroke-like syndrome.

BACKGROUND:In 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. METHODS:We 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. RESULTS:Sixty-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. CONCLUSIONS:This 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

Epidemiology and aetiologies of cryptococcal meningitis in Africa, 1950-2017: protocol for a systematic review.

IntroductionCryptococcal meningitis is a neglected disease and an AIDS-defining illness, responsible for 15% of all AIDS-related deaths globally. In 2014, the estimated number of incident cryptococcal meningitis cases was 223 100, with 73% of them occurring in Africa. Currently available data on the prevalence, incidence, aetiologies and mortality of cryptococcal meningitis across Africa are sparse and of limited quality. We propose to conduct the first systematic review to summarise the epidemiological data available on cryptococcal meningitis and its aetiological causes in Africa.Methods and analysisWe will search PubMed, MEDLINE, Excerpta Medica Database, ISI Web of Science, Africa Index Medicus, Cumulative Index to Nursing and Allied Health for studies on cryptococcal meningitis published between 1st January 1950 and 31st December 2017, involving adults and/or children residing in Africa. After study selection, full text paper acquisition and data extraction, we will use validated tools and checklists to assess the quality of reporting and risk of bias for each study. Heterogeneity across studies will be assessed using the χ2 test on Cochrane's Q statistic and a random effect meta-analysis will be used to estimate the overall prevalence, incidence density and mortality of cryptococcal meningitis across studies with similar characteristics. This protocol is prepared and presented in accordance with the 2015 Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines. Reporting of the results will be compliant with the Meta-Analysis Of Observational Studies in Epidemiology (MOOSE) guidelines.Ethics and disseminationThere is no requirement for ethical approval since we will be using data from published studies. The final report will be published in a peer-reviewed journal and further presented at conferences. This study is expected to provide useful contextual estimates needed to inform treatment policies on the African continent and assess the impact of diagnostic and prevention strategies on the burden of cryptococcal meningitis in the post antiretroviral therapy era.Prospero registration numberCRD42017081312

Challenges of stroke management in resource-limited settings: A case- based reflection

A 19-year-old man presented with a 1-year history of headache, generalised body weakness, progressive memory loss, and disorientation. One month prior to admission, there was aggravation of the weakness of the right upper limb, with new-onset difficulty with mastication, speech impairment, apathy, and urinary incontinence. On clinical examination, the patient had a motor aphasia and a right-sided hemiparesis with increased muscle tone and hyperreflexia. A noncontrast computed tomography (CT) scan of the brain revealed large ischaemic strokes extending beyond the classical vascular territories. Cerebrospinal fluid analysis showed a mildly increased protein level. The electrocardiogram revealed an irregular sinus bradycardia. The remainder of the cardiovascular and laboratory workup was unremarkable. Considering a working diagnosis of central nervous system vasculitis, the patient was treated with aspirin, prednisolone, and physiotherapy. However, he died suddenly a few weeks later. Based on this case, we discuss the challenges of stroke management in resource-limited settings, provide practical tips for general practitioners, reflect on the potential avenues for short- and long-term action, and introduce the budding collaboration platform between the University College London, the University of Liverpool, the Queen Elizabeth Central Hospital, and the Malawi-Liverpool-Wellcome Trust Clinical Research Programme