Genetic Epidemiology and Associated Diseases of APOL1: A Narrative Review.

BACKGROUND: The Apolipoprotein 1 (APOL1) protein is a product of the human APOL1 gene located on chromosome 22q13.1 and performs functions including lipid transport and metabolism, programmed cell death, autophagy and innate immunity against intracellular pathogens. It is unique among its gene family in its possession of a signal peptide that confers on it the ability for export out of the cell and into the blood stream. The aim of this review is to explore the genetic epidemiology and biology of the APOL1 gene, describe its association with different renal and extra-renal disorders and highlight the timelines of the discoveries of the various associations. METHODS: A literature search was carried out using combination of terms including "apolipoproteins", "apolipoprotein L", "APOL1", "genetics of APOL1", "Chronic Kidney Disease (CKD) and APOL1"," APOL1 and associated diseases" covering the period January 1990 to April 2020. RESULTS: High frequency of the APOL1 gene arose as a result of natural selection in East and West Africa, regions endemic for Trypanosoma brucei infection. High frequencies are also reported among individuals of African ancestry in North America. APOL1 G1 and G2 variants protect against Trypanosoma brucei rhodesiense having overcome their virulence through the serum trypanolytic factor. Although protective against infection from trypanosomes, these alleles have also been shown to increase the risk of several disorders including various forms of chronic kidney diseases, schizophrenia, stroke, cancer, and pre - eclampsia. CONCLUSION: The elucidation of the APOL1 gene has deepened understanding of racial disparities in health and disease. Growing understanding of the genetics and functions of APOL1 has potential to enhance translational benefits for development of new biomarkers, preventive and therapeutic interventions in the context of precision medicine.

RÉSUMÉ: La protéine Apolipoprotéine 1 (APOL1) est un produit du gène humain APOL1 situé sur le chromosome 22q13.1 et remplit des fonctions telles que le transport et le métabolisme des lipides, la mort cellulaire programmée, l'autophagie et l'immunité innée contre les agents pathogènes intracellulaires. Il est unique parmi sa famille de gènes en ce qu'il possède un peptide signal qui lui confère la capacité de s'exporter hors de la cellule et dans la circulation sanguine. L'objectif de cette revue est d'explorer l'épidémiologie génétique et la biologie du gène APOL1, de décrire son association avec différentes maladies rénales et extra-rénales et de mettre en évidence la chronologie des découvertes des différentes associations. MÉTHODES: Une recherche bibliographique a été effectuée en utilisant une combinaison de termes comprenant « apolipoprotéines ¼, « apolipoprotéine L ¼, « APOL1 ¼, « génétique d'APOL1 ¼, « Maladie rénale chronique (CKD) et APOL1 ¼, « APOL1 et maladies associées ¼ période de janvier 1990 à avril 2020. RÉSULTATS: La fréquence élevée du gène APOL1 est apparue à la suite de la sélection naturelle en Afrique de l'Est et de l'Ouest, régions endémiques pour l'infection à Trypanosoma brucei. Des fréquences élevées sont également signalées chez les individus d'ascendance africaine en Amérique du Nord. Les variants APOL1 G1 et G2 protègent contre Trypanosoma brucei rhodesiense après avoir surmonté leur virulence grâce au facteur trypanolytique sérique. Bien qu'ils protègent contre l'infection par les trypanosomes, il a également été démontré que ces allèles augmentent le risque de plusieurs troubles, notamment diverses formes de maladies rénales chroniques, la schizophrénie, les accidents vasculaires cérébraux, le cancer et la pré-éclampsie. CONCLUSION: L'élucidation du gène APOL1 a approfondi la compréhension des disparités raciales en matière de santé et de maladie. La compréhension croissante de la génétique et des fonctions d'APOL1 a le potentiel d'améliorer les avantages translationnels pour le développement de nouveaux biomarqueurs, d'interventions préventives et thérapeutiques dans le contexte de la médecine de précision. MOTS-CLÉS: APOL1 ; La génétique; Épidémiologie; La biologie; Maladies associées.

Prevalence and Correlates of Frailty Syndrome among Older Adults Attending Chief Tony Anenih Geriatric Centre, University College Hospital, Ibadan.

BACKGROUND: Frailty has emerged as an important clinical measurement among older adults because of its negative health outcomes. OBJECTIVE: This study measured the prevalence and factors associated with frailty among older adults aged 60 years and above at a Geriatric Centre in Nigeria. METHODS: In this descriptive cross-sectional study, 971 older adults were recruited consecutively. Data on sociodemographics characteristics and clinical parameters were obtained using an interviewer-administered questionnaire and physical examination performed. The Frailty syndrome and Frailty Index were assessed using the Fried Frailty Criteria (FFC) and Canadian Study of Health and Aging (CSHA) scale respectively. Bivariate and multivariate analyses were carried out using SPSS version 21 at a p <0.05. RESULTS: The mean age of the participants was 71.3 (± 7.1) years with a female to male ratio of 2.4:1. Based on FFC scale, 498 older persons (51.3%) had frailty syndrome while only 148 (15.2%) were frail using the CSHA scale. The measure of agreement (Kappa statistics) was 0.22 (p<0001) indicating weak agreement between the two scales. Logistic regression analysis revealed increasing age (OR=1.948 [1.219-3.113]), multiple morbidities (OR= 1.584, [1.177-2.201]), depression (OR= 5.050, [2.501-9.442,]), imbalance or increased risk of fall (OR 1.623, [1.192-2.211,]), and inability to perform IADL (OR= 0.599 [0.535-0.670,]) to be the most significant determinants of frailty syndrome while obesity (OR=0.660, [0.449-0.971]), unusually appeared a deterrent. CONCLUSION: The prevalence of frailty syndrome was high among the older adults. Targeted and timely interventions on the modifiable factors may delay progression into frailty and the eventual negative health outcomes.

CONTEXTE: La fragilité a ete emerge comme un élément clinique important mesure chez les personnes âgées en raison de son état de santé négatif les résultats. OBJECTIF: Cette étude a mesuré la prévalence et les facteurs associée à la fragilité chez les personnes âgées de 60 ans et cidessus dans un centre gériatrique au Nigéria. MÉTHODES: Dans cette étude transversale descriptive, 971 des adultes plus âgés ont été recrutés consécutivement. Les données sur les caractéristiques sociodémographiques et les paramètres cliniques ont été obtenu à l'aide d'un questionnaire administré par l'enquêteur et un examen physique effectué. Le syndrome de fragilité et l'indice de fragilité ont été évalués à l'aide du Fried Frailty Critères (FFC) et étude canadienne sur la santé et le vieillissement (CSHA) respectivement. Bivarié et multivarié les analyses ont été réalisées à l'aide de SPSS version 21 à p <0,05. RÉSULTATS: L'âge moyen des participants était de 71,3 (± 7,1) ans avec un ratio femmes / hommes de 2,4: 1. Basé sur l'échelle FFC, 498 personnes âgées (51,3%) avaient un syndrome de fragilité alors que seulement 148 (15,2%) étaient fragiles selon l'échelle de la SCVS. La mesure d'accord (statistiques Kappa) était de 0,22 (p <0001) indiquant faible accord entre les deux échelles. Une analyse de régression logistique a révélé une augmentation de l'âge (OR = 1,948 [1,219-3,113]), morbidités multiples (OR = 1,584, [1.177-2.201]), dépression (OR = 5.050, [2.501-9.442,]), déséquilibre ou risque accru de chute (OR 1.623, [1.192-2.211,]), et l'incapacité d'effectuer une IADL (OR = 0,599 [0,535-0,670,]) pour être les déterminants les plus importants du syndrome de fragilité obésité (OR = 0,660, [0,449-0,971]), apparaissait inhabituellement dissuasif. CONCLUSION: La prévalence du syndrome de fragilité était élevée parmi les personnes âgées. Interventions ciblées et opportunes sur les facteurs modifiables peuvent retarder la progression vers la fragilité et les éventuels effets négatifs sur la santé. Mots clés: Syndrome de fragilité; Corrélats; Les adultes plus âgés; Gériatrie.

DELAYED DIAGNOSIS OF AVM PRESENTING WITH STROKE AND SEIZURES IN A YOUNG NIGERIAN: A CASE REPORT.

Background: Brain arteriovenous malformations (BAVM) are a cause of intracerebral haemorrhage (ICH) and seizures especially in young patients. ICH due to BAVMs seem to have relatively better neurologic outcomes compared to other causes of spontaneous ICH as patients often recover fully. In this report we highlight a case of delayed diagnosis of BAVM in a young man who presented with seizures and stroke. Case summary: A 36-year-old man was referred on account of focal, secondarily generalized tonic clonic convulsions. He had suffered a right ICH 3 years before the index presentation. His general physical and neurologic examination were normal. Electroencephalography revealed right sided focal epileptiform discharges and brain MRI revealed a right parieto-occipital AVM. The seizures were controlled with carbamazepine and he was referred for neurosurgical evaluation. Conclusion: BAVMs are an important cause of intracerebral haemorrhage and attendant neurologic morbidity especially in young individuals. Neuroimaging plays a central role in BAVM diagnosis and MRI is of great value where facilities and expertise for conventional angiography do not exist. In some instances, delayed presentation of BAVM cases may be due to relatively better neurologic outcomes in BAVM-related ICH.

Tropical ataxic neuropathy: Findings of a neuroepidemiological survey of Odeda, southwest Nigeria.

BACKGROUND: Tropical ataxic neuropathy seems to have dwindled in public health importance in Nigeria despite the high consumption of cassava-based meals by a huge proportion of people in local Nigerian communities. Yet a recent report suggest its persistence in the same ethnogeographic setting where it was first reported in Nigeria. Our objective was to investigate the prevalence of tropical ataxic neuropathy in Odeda, Ogun state, southwest Nigeria inhabited by a different ethnic group compared to Epe where the disease was first described. METHODS: A two-stage, cross-sectional survey of Odeda local government area for the prevalence and profile of toxiconutritional neurological disorders was carried out between May and June 2015. A screening instrument was applied by trained non - medical interviewers with positive responders further evaluated by a neurologist. RESULTS: 2392 individuals aged 18 years or older were screened and had a mean age of 37.2 ±â€¯16.1 years, were predominantly of Egba Yoruba ethnicity. Thirty nine cases of tropical ataxic neuropathy were diagnosed and crude prevalence rate was 16.3/1000 (95% CI 11.2-21.4/1000). Older age and rural residence were associated with higher prevalence. Distal sensory polyneuropathy was the most common feature whereas sensorineural deafness was the least common finding. CONCLUSION: This report provides evidence that tropical ataxic neuropathy persists and in a wider geographic spread. Thus tropical ataxic neuropathy still remains a significant public health importance and concerted efforts are required to mitigate or eradicate tropical ataxic neuropathy in southwest Nigeria and other regions of Africa affected by cassava- related toxiconutritional disorders.

Stroke genomics in people of African ancestry: charting new paths.

One in six people worldwide will experience a stroke in his/her lifetime. While people in Africa carry a disproportionately higher burden of poor stroke outcomes, compared to the rest of the world, the exact contribution of genomic factors to this disparity is unknown. Despite noteworthy research into stroke genomics, studies exploring the genetic contribution to stroke among populations of African ancestry in the United States are few. Furthermore, genomics data in populations living in Africa are lacking. The wide genomic variation of African populations offers a unique opportunity to identify genomic variants with causal relationships to stroke across different ethnic groups. The Stroke Investigative Research and Educational Network (SIREN), a component of the Human Health and Heredity in Africa (H3Africa) Consortium, aims to explore genomic and environmental risk factors for stroke in populations of African ancestry in West Africa and the United States. In this article, we review the literature on the genomics of stroke with particular emphasis on populations of African origin.

Seizure severity and health-related quality of life of adult Nigerian patients with epilepsy.

OBJECTIVES: There is paucity of information about the association of seizure severity and quality of life in people with epilepsy (PWE) in sub-Saharan Africa. We evaluated the relationship of seizure severity to health-related quality of life of patients with epilepsy being followed up in an outpatient neurology clinic in southwestern Nigeria. MATERIALS AND METHODS: Eighty-eight consecutive patients with epilepsy who met the recruitment criteria completed the study questionnaire in company of an eyewitness. The study questionnaire comprised of the National Hospital Seizure Severity Scale (NHS3), the Quality of Life Inventory in Epilepsy (QOLIE-31), and the Beck's Depression Inventory-II (BDI-II). RESULTS: We found a minute association between seizure severity and QOLIE-31 total score (r = -0.262, P = 0.014). Increased seizure severity predicted a worse QOLIE-31 seizure worry (R(2) = 0.311, ß = -0.289; P = 0.003). Of the seven seizure severity items, generalization of seizures and presence of falls were items that predicted a worse QOLIE-31 seizure worry score and time to recover predicted a worse QOLIE-31 total score. CONCLUSIONS: Reducing seizure severity may be an alternate endpoint in epilepsy care in Nigeria (particularly difficult to control seizures) because of its practical clinical relevance in view of the fact that state-of-the-art epilepsy care is still farfetched.

Neuropsychiatric symptoms in Nigerian patients with Parkinson's disease.

BACKGROUND: Neuropsychiatric symptoms are common in Parkinson's disease and may precede onset of motor symptoms. They are also known to increase caregiver's burden. OBJECTIVE: The aim of this study was to assess neuropsychiatric symptoms in a cohort of Nigerian patients with idiopathic Parkinson's disease and compare with systemic hypertension. METHOD: Fifty patients with idiopathic Parkinson's disease were compared with fifty demographically matched controls with systemic hypertension. Diagnosis of Parkinson's disease was based on the United Kingdom Parkinson Disease Society (UKPDS) Brain Bank Clinical diagnostic Criteria. Diagnosis of hypertension was based on recorded blood pressure of ≥140/90 mmHg on two different occasions. The Neuropsychiatric Inventory (NPI) was applied to caregivers of both patients and controls. RESULTS: There were significant differences in frequency of neuropsychiatric symptoms in patients and controls (P < 0.05). Significant differences were found in mean distress scores for some neuropsychiatric symptoms and the total mean distress score. In all cases, patients with Parkinson's disease had higher scores when compared with controls. Severity of motor symptoms, as measured by the UKPDS, correlated with total NPI severity scores (P = 0.000). CONCLUSION: Neuropsychiatric symptoms occur more frequently in Parkinson's disease than matched controls, and the presence of these symptoms is associated with caregivers' distress. There is a need for early and adequate treatment for motor and behavioural symptoms of Parkinson's disease.

Cerebral amyloid ß(42) deposits and microvascular pathology in ageing baboons.

BACKGROUND: Previous studies have extensively reported the deposition of amyloid ß (Aß) peptide with carboxyl- and amino-terminal heterogeneity in cortical and cerebrovascular deposits in Alzheimer's disease (AD) and in non-human primates except baboons. METHODS: We examined the immunocytochemical distribution of Aß peptides and Aß oligomers in brain tissue from three subspecies of 18- to 28-year-old baboons (Papio) and in other monkeys including the squirrel (Saimiri sciureus) and rhesus (Macaca mulatta) for comparison. RESULTS: A general preponderance of Aß(42) in parenchymal deposits and many vascular deposits in all cortical lobes was evident in the baboons. Aß oligomeric immunoreactivity was also apparent like to amyloid plaques. We found that the amino acid sequence of the Aß domain of the baboon amyloid precursor protein is similar to that of man. In contrast to Aß, immunoreactivity to hyperphosphorylated tau protein was largely intracellular and rare in these baboons. Brain tissues from squirrel and rhesus monkeys examined in parallel exhibited mostly vascular and parenchymal deposits containing Aß(42) peptides. Our results were comparable to AD, but showed that even in younger monkeys exhibiting few deposits, Aß(42) was evident in both parenchymal deposits and cerebral amyloid angiopathy. Perivascular amyloid deposits were frequent and often accompanied by microvascular abnormalities in the form of collapsed degenerated capillaries. CONCLUSIONS: Similar to other primates above and below in the phylogenetic order, our observations and evaluation of the literature implicate pathogenicity of Aß(42) peptide associated with microvascular degeneration in baboons. We suggest baboons are useful animals to investigate the dynamics of AD-related pathology.

Profile of clinically-diagnosed dementias in a neuropsychiatric practice in Abeokuta, south-western Nigeria.

OBJECTIVE: Many subjects with dementia present primarily to neuropsychiatric practices because of behavioural and psychological symptoms (BPSD). This study reviewed the profile of clinically-diagnosed dementias and BPSD seen in a pioneer neuropsychiatric practice in Abeokuta, southwestern Nigeria over a ten year period (January1998 - December 2007). METHODS: A review of hospital records of all patients with diagnoses of dementia or dementing illness using the ICD-10 criteria as well as specific diagnostic criteria for different dementia phenotypes. Associated BPSD, co-morbidities and treatments were also reviewed. RESULTS: Out of a total of 240,294 patients seen over the study period, 108 subjects met clinical diagnostic criteria for probable dementia giving a hospital frequency of 45 per 100,000. Alzheimer's disease (AD) and Vascular dementia (VaD) were the predominant phenotypes seen in 62 (57.4%) and 18 (16.7%) subjects respectively. Others include mixed dementia (4 cases), frontotemporal dementia (4 cases), Lewy body dementia (3 cases), alcohol-related dementia (3 cases), PD dementia (1 case) and unclassifiable (13 cases). Apathy, night time behaviour, aberrant motor behaviour, agitation and irritability were the most common BPSD features, while hypertension was the most common co-morbidity. Neuroleptics, anticholinergics and anti-hypertensives were most commonly prescribed. Anticholinesterase inhibitors were sparingly used. CONCLUSION: Probable AD was the most prevalent dementia phenotype seen in this practice. Increased awareness of dementia and better utilization of specific treatments are needed among psychiatrists and primary care practitioners in Nigeria.

Prevalence of asymptomatic left ventricular systolic dysfunction in hypertensive Nigerians: echocardiographic study of 832 subjects.

BACKGROUND: We sought to determine the prevalence of echocardiographically determined left ventricular systolic dysfunction in asymptomatic hypertensive subjects seen in Abeokuta, Nigeria. METHODS: Echocardiography was performed in 832 consecutive hypertensive subjects referred for cardiac evaluation over a three-year period. RESULTS: Data were obtained in 832 subjects (50.1% women) aged 56.0 ± 12.7 years (men 56.9 ± 13.3 years, women 55.0 ± 12.0 years, range 15-88). The prevalence of left ventricular systolic dysfunction (LVSD) was 18.1% in the study population (mild LVSD = 9.6%, moderate LVSD = 3.7% and severe LVSD = 4.8%). In a multivariate analysis, male gender, body mass index and LV mass were the predictors of LVSD. CONCLUSION: Significant numbers of hypertensive subjects in this study had varying degrees of left ventricular systolic dysfunction. Early introduction of disease-modifying drugs in these patients, such as angiotensin converting enzyme inhibitors or angiotensin receptor blockers may retard or prevent the progression to overt heart failure.

Frontotemporal dementia in a Nigerian woman: case report and brief review of the literature.

Frontotemporal lobal degeneration (FTLD) is a clinically heterogeneous group of sporadic and familial neurodegenerative diseases characterized by dementia, alteration in language and/or behaviour, loss of executive skills and sometimes Parkinsonian features resulting from degeneration predominantly affecting the anterior frontal and temporal regions of the brain. Three main clinical subtypes including frontotemporal dementia (FTD), semantic dementia (SD) and progressive non-fluent aphasia (PNFA) have been described depending on the clinical phenomenology, the areas of the brain where the disorder begins and where the most extensive degeneration occurs. We describe a case of frontotemporal dementia in a 58 year old Nigerian woman and also review the current literature. Recent genetic studies have expanded the frontiers of knowledge about FTD while the search for appropriate drug treatments continues.

Knowledge and perception of stroke amongst hospital workers in an African community.

BACKGROUND AND PURPOSE: Stroke is a growing public health problem worldwide. Hospital workers are sources of knowledge on health issues including stroke. The present study aimed at assessing the knowledge and perception of a sample of Nigerian hospital workers about stroke. METHODS: Hospital-based, cross-sectional survey. Respondents selected by systematic random sampling were interviewed using a 29-item pre-tested, structured, semi-closed questionnaire. RESULTS: There were 370 respondents (63% female, mean age: 34.4 +/- 7.5 years; 61% non-clinical workers). Twenty-nine per cent of respondents did not recognize the brain as the organ affected. Hypertension (88.6%) was the commonest risk factor identified; 13.8% identified evil spirit/witchcraft as a cause of stroke, whilst one-sided body weakness (61.9%) was most commonly identified as warning symptom. Hospital treatment was most preferred by 61.1% of respondents whilst spiritual healing was most preferred by 13.0%. In the bivariate analysis, higher level of education and being a clinical worker correlated with better stroke knowledge (P < 0.001). CONCLUSION: This study demonstrates gaps in the knowledge of these hospital workers about stroke, and treatment choice influenced by cultural and religious beliefs. Health education is still important, even, amongst health workers and stroke awareness campaigns may need to involve faith-based organizations.

Unusual presentation of thyrotoxicosis--a case report and review of literature.

BACKGROUND: The majority of patients with thyrotoxicosis are readily diagnosed clinically. It must be accepted however that not every patient presents with the characteristic picture. Thyrotoxicosis occasionally presents in an unknown or atypical fashion in which the diagnosis may not be obvious. CASE REPORT: A 45-year-old woman presented with choreoathetoid movements of the right upper limb, persistent vomiting and generalized body weakness. Over the next few weeks, the clinical picture slowly evolved to give the characteristic symptoms and signs of thyrotoxicosis, which were not evident at presentation. Thyroid function tests revealed elevated serum thyroxine and triiodothyronine as well as low thyroid stimulating hormone concentrations, confirming the diagnosis of thyrotoxicosis. CONCLUSION: This case illustrates unusual initial presenting features of thyrotoxicosis, which long preceded the development of the characteristic and more common manifestations. This led to a delay in the diagnosis. Awareness of these atypical presentations will further assist the physician to make a timely and cost effective diagnosis of this condition.