Profile, determinants and mechanisms of cerebral injury and cognitive impairment following stroke

PhD ThesisOne in three people over a life time will develop a stroke, dementia or both but little is known about stroke - related cognitive impairment despite current epidemiologic transition in sub - Saharan Africa. The CogFAST Study was established in Newcastle to unmask risk factors, pathological substrates and cellular mechanisms underlying cerebral injury and cognitive impairment following stroke. The overall aim of this thesis was to establish a comparative cohort in Nigerian African stroke survivors and explore mechanisms in post - mortem brains accrued from the Newcastle cohort. Two hundred and twenty Nigerian African stroke survivors were screened three months after index stroke out of whom 143 eligible participants underwent cognitive assessment in comparison with 74 stroke - free healthy controls. We found a high frequency (49.3%) of early vascular cognitive impairment and significant association with older age and low education. Pre-stroke daily fish intake and moderate – to - heavy physical activity were inversely associated. The frequency of vascular cognitive impairment no dementia (vCIND) in the cohort (39.9%) was relatively higher than earlier report from Newcastle (32%) but neuroimaging studies revealed significant findings of MTLA and correlative white matter changes in tandem with previous reports from the Newcastle cohort. Given these, we investigated neurodegenerative hippocampal Alzheimer pathology and synaptic changes, as well as frontal and temporal white matter abnormalities in post - mortem brain tissue from the Newcastle cohort. We found increased Alzheimer pathology in the post - stroke groups but largely this did not differ between the demented (PSD) and non - demented (PSND) sub - groups. However, we found significantly higher hippocampal expression of synaptic markers (vesicular glutamate transporter – 1 and Drebrin) but lower expression of microglial, astrocytic and axonal injury markers in PSND compared to PSD subjects. The protective effect of educational attainment, pre-stroke physical activity and fish intake have public brain health implications.ORS Award from Newcastle University, a Research Fellowship from the International Brain Research Organization (IBRO) and laboratory visit support from the International Society of Neurochemistry (ISN)

Stroke injury, cognitive impairment and vascular dementia

AbstractThe global burden of ischaemic strokes is almost 4-fold greater than haemorrhagic strokes. Current evidence suggests that 25–30% of ischaemic stroke survivors develop immediate or delayed vascular cognitive impairment (VCI) or vascular dementia (VaD). Dementia after stroke injury may encompass all types of cognitive disorders. States of cognitive dysfunction before the index stroke are described under the umbrella of pre-stroke dementia, which may entail vascular changes as well as insidious neurodegenerative processes. Risk factors for cognitive impairment and dementia after stroke are multifactorial including older age, family history, genetic variants, low educational status, vascular comorbidities, prior transient ischaemic attack or recurrent stroke and depressive illness. Neuroimaging determinants of dementia after stroke comprise silent brain infarcts, white matter changes, lacunar infarcts and medial temporal lobe atrophy. Until recently, the neuropathology of dementia after stroke was poorly defined. Most of post-stroke dementia is consistent with VaD involving multiple substrates. Microinfarction, microvascular changes related to blood–brain barrier damage, focal neuronal atrophy and low burden of co-existing neurodegenerative pathology appear key substrates of dementia after stroke injury. The elucidation of mechanisms of dementia after stroke injury will enable establishment of effective strategy for symptomatic relief and prevention. Controlling vascular disease risk factors is essential to reduce the burden of cognitive dysfunction after stroke. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock

Menstrual-Related Headaches Among a Cohort of African Adolescent Girls

Introduction: Migraine attacks associated with menstruation are generally perceived as more severe than attacks outside this period. Aim and Objective: The study aimed at determining the frequency of menstrual-related headaches among a cohort of senior secondary school girls in Abeokuta, Nigeria. We also determined its burden among these school girls. Methodology: This study was cross-sectional using a validated adolescent headache survey questionnaire. A self-administration of the instrument was done during a school visit. A headache was classified using the ICHD-II criteria. Results: Of the 183 students interviewed, 123(67.2%) had recurrent headaches. Mean age ±SD, 16.18± 1.55 (range 12– 19). The prevalence of definite migraine was 17.5% while the prevalence of probable migraine was 6.0%. The prevalence of tension-type headache was 41.0%. Migraine was significantly menstrual-related (p=0.001, 95% CI=1.06– 6.63). Median pain severity score was higher among MRH group (p=0.043). The median number of days of reduced productivity and missed social activities was significantly higher in the MRH group; p= 0.001 and p=0.03, respectively. Subjects with MRH were more incapacitated by their headaches (p= 0.003). Conclusion: Menstrually related headache is prevalent even among the adolescent and it has adversely affected their productivity and social life. Care of adolescent with headaches should be intensified

Graves’ disease presenting as paranoid schizophrenia in a Nigerian woman: a case report

Paranoid syndromes in Graves’ disease are rare. The true incidence is lacking. Most reports have emanated from developed countries where medical investigations are readily available. No report of such has emanated from Nigeria. We report a 43-year-old female Nigerian with Graves’ disease associated with paranoid schizophrenia and review the literature

Advancing Stroke Genomic Research in the Age of Trans-Omics Big Data Science: Emerging Priorities and Opportunities

Background—We systematically reviewed the genetic variants associated with stroke in genome-wide association studies (GWAS) and examined the emerging priorities and opportunities for rapidly advancing stroke research in the era of Trans-Omics science. Methods—Using the PRISMA guideline, we searched PubMed and NHGRI- EBI GWAS catalog for stroke studies from 2007 till May 2017. Results—We included 31 studies. The major challenge is that the few validated variants could not account for the full genetic risk of stroke and have not been translated for clinical use. None of the studies included continental Africans. Genomic study of stroke among Africans presents a unique opportunity for the discovery, validation, functional annotation, trans-omics study and translation of genomic determinants of stroke with implications for global populations. This is because all humans originated from Africa, a continent with a unique genomic architecture and a distinctive epidemiology of stroke; as well as substantially higher heritability and resolution of fine mapping of stroke genes. Conclusion—Understanding the genomic determinants of stroke and the corresponding molecular mechanisms will revolutionize the development of a new set of precise biomarkers for stroke prediction, diagnosis and prognostic estimates as well as personalized interventions for reducing the global burden of stroke

Spectrum of heart diseases in a new cardiac service in Nigeria: An echocardiographic study of 1441 subjects in Abeokuta

<p>Abstract</p> <p>Background</p> <p>Echocardiography is a non-invasive, relatively cheap and useful imaging technique for the evaluation of cardiac diseases. The procedure has reliable levels of accuracy.</p> <p>Echocardiography commenced at the Federal medical centre Abeokuta on September 9, 2005.</p> <p>The aim of this study is to report our experience with the procedure, and to define the clinical cases seen in our setting.</p> <p>Methods</p> <p>This is a retrospective analysis of a prospectively collected data. Echocardiography was performed using Aloka SSD 1,100 echocardiograph equipped with 2.5–5.0 MHz transducer</p> <p>Results</p> <p>During the period of 18 months under review (September 2005–February 2007), 1629 procedures were performed. The reports of 188 echocardiograms were excluded due to poor echo-window, repeated procedure or incomplete report. 1441 reports were reviewed for demographic parameter, indications for the procedure and the main echocardiographic diagnoses.</p> <p>The mean age of the 1441 individuals studied was 54 +/- 14.3 years (15–90). There were 744 men and 697 women. Eight hundred and seventeen subjects (56.7%) had hypertensive heart disease, 53 subjects (3.7%) had rheumatic heart disease while 44(3.0%) had dilated cardiomyopathy. Pericardial diseases, cor-pulmonale, ischaemic heart disease, congenital heart diseases, diabetic heart disease, thyroid heart disease, sickle cell cardiopathy were present in 26(1.8%), 23(1.6%), 9(0.6%), 6(0.4%), 6(0.4%), 6(0.4%), 1(0.1%), and 1(0.1%) respectively. Four hundred and forty nine (31.2%) subjects had normal study.</p> <p>Conclusion</p> <p>Hypertensive heart disease was found to be the most prevalent cardiac condition in this study. The relatively frequent diagnoses of rheumatic heart disease, cardiomyopathies and pericardial diseases reflect the impact of infections and infestations on the cardiovascular health of adult Nigerians.</p> <p>We suggest that prevention and treatment of cardiac diseases in our setting should among other things focus on blood pressure control and early treatment of infections causing heart diseases.</p

Stroke in Africa: a systematic review and meta-analysis of the incidence and case-fatality rates

Background: The burden of stroke (a leading cause of disability and mortality) in Africa appears to be increasing, but a systematic review of the best available data to support or refute this observation is lacking. Aim: To determine the incidence and one-month case-fatality rates from high-quality studies of stroke epidemiology among Africans. Summary of review : We searched and retrieved eligible articles on stroke epidemiology among indigenous Africans in bibliographic databases (PubMed, ScienceDirect, Google Scholar and Cochrane library) using predefined search terms from the earliest records through January 2022. Methodological assessment of eligible studies was conducted using the Newcastle-Ottawa scale. Pooling of incidence and case-fatality rates was performed via generalized linear models (Poisson-Normal random-effects model). Of the 922 articles retrieved, fourteen studies were eligible for inclusion. The total number of stroke cases was 5,104 (mean: 365 SD: 254) with a population denominator (total sample size included in population-based registries or those who agreed to participate in door-to-door community studies) of 3,638,304. The pooled crude incidence rate of stroke per 100,000 persons in Africa was 106.49 (95% CI 58.59–193.55), I2 = 99.6%. The point estimate of the crude incidence rate was higher among males, 111.33 (95% CI 56.31–220.12), I2 = 99.2% than females, 91.14 (95% CI 47.09–176.37), I2 = 98.9%. One–month case-fatality rate was 24.45 (95% CI 16.84–35.50), I2 = 96.8% with lower estimates among males, 22.68 (95% CI 18.62–27.63), I2 = 12.9% than females, 27.57 (95% CI 21.47–35.40), I2 = 51.6%. Conclusions: The burden of stroke in Africa remains very high. However, little is known about the dynamics of stroke epidemiology among Africans due to the dearth of high-quality evidence. Further continent-wide rigorous epidemiological studies and surveillance programs using the World Health Organization STEPwise approach to Surveillance (WHO STEPS) framework are needed

Loss of capillary pericytes and the blood–brain barrier in white matter in poststroke and vascular dementias and Alzheimer’s disease

White matter (WM) disease is associated with disruption of the gliovascular unit, which involves breach of the blood‐brain barrier (BBB). We quantified pericytes as components of the gliovascular unit and assessed their status in vascular and other common dementias. Immunohistochemical and immunofluorescent methods were developed to assess the distribution and quantification of pericytes connected to the frontal lobe WM capillaries. Pericytes with a nucleus were identified by collagen 4 (COL4) and platelet derived growth factor receptor‐β (PDGFR‐β) antibodies with further verification using PDGFR‐β specific ELISA. We evaluated a total of 124 post‐mortem brains from subjects with post‐stroke dementia (PSD), vascular dementia (VaD), Alzheimer’s disease (AD), AD‐VaD (Mixed), and post‐stroke non‐demented (PSND) stroke survivors as well as normal ageing controls. COL4 and PDGFR‐β reactive pericytes adopted the characteristic “crescent” or nodule‐like shapes around capillary walls. We estimated densities of pericyte somata to be 225 ±38 and 200 ±13 (SEM) per COL4 mm2 area or 2.0 ±0.1 and 1.7 ±0.1 per mm capillary length in young and older ageing controls. Remarkably, WM pericytes were reduced by ~35‐45 percent in the frontal lobe of PSD, VaD, Mixed and AD subjects compared to PSND and controls subjects (P&lt;0.001). We also found pericyte numbers were correlated with PDGFR‐β reactivity in the WM. Our results first demonstrate a reliable method to quantify COL4‐positive pericytes and then indicate that deep WM pericytes are decreased across different dementias including PSD, VaD, Mixed and AD. Our findings suggest that down regulation of pericytes is associated with the disruption of the BBB in the deep WM in several ageing‐related dementias

Exploring Overlaps Between the Genomic and Environmental Determinants of LVH and Stroke: A Multicenter Study in West Africa

Background Whether left ventricular hypertrophy (LVH) is determined by similar genomic and environmental risk factors with stroke, or is simply an intermediate stroke marker, is unknown. Objectives We present a research plan and preliminary findings to explore the overlap in the genomic and environmental determinants of LVH and stroke among Africans participating in the SIREN (Stroke Investigative Research and Education Network) study. Methods SIREN is a transnational, multicenter study involving acute stroke patients and age-, ethnicity-, and sex-matched control subjects recruited from 9 sites in Ghana and Nigeria. Genomic and environmental risk factors and other relevant phenotypes for stroke and LVH are being collected and compared using standard techniques. Results This preliminary analysis included only 725 stroke patients (mean age 59.1 ± 13.2 years; 54.3% male). Fifty-five percent of the stroke subjects had LVH with greater proportion among women (51.6% vs. 48.4%; p \u3c 0.001). Those with LVH were younger (57.9 ± 12.8 vs. 60.6 ± 13.4; p = 0.006) and had higher mean systolic and diastolic blood pressure (167.1/99.5 mm Hg vs 151.7/90.6 mm Hg; p \u3c 0.001). Uncontrolled blood pressure at presentation was prevalent in subjects with LVH (76.2% vs. 57.7%; p \u3c 0.001). Significant independent predictors of LVH were age \u3c45 years (adjusted odds ratio [AOR]: 1.91; 95% confidence interval [CI]: 1.14 to 3.19), female sex (AOR: 2.01; 95% CI: 1.44 to 2.81), and diastolic blood pressure \u3e 90 mm Hg (AOR: 2.10; 95% CI: 1.39 to 3.19; p \u3c 0.001). Conclusions The prevalence of LVH was high among stroke patients especially the younger ones, suggesting a genetic component to LVH. Hypertension was a major modifiable risk factor for stroke as well as LVH. It is envisaged that the SIREN project will elucidate polygenic overlap (if present) between LVH and stroke among Africans, thereby defining the role of LVH as a putative intermediate cardiovascular phenotype and therapeutic target to inform interventions to reduce stroke risk in populations of African ancestry