Assessment of sleep knowledge among medical and dental students in a Nigerian tertiary institution: a cross-sectional study.

PURPOSE: Sleep medicine is a rapidly growing field of Medicine globally. However, studies are lacking on the knowledge of Nigerian medical and dental students on sleep and the different types of sleep disorders. Thus, we assessed the knowledge, interest and awareness of Nigerian medical and dental students about sleep medicine. We also determined the factors associated with sleep knowledge among the medical and dental students. METHODS: We conducted this cross-sectional study from June to September 2021, among medical students at the Obafemi Awolowo University, Ile-Ife, Nigeria. The students' knowledge of sleep was assessed with the Assessment of Sleep Knowledge in Medical Education (ASKME) survey. The participants were classified as having low or high scores based on the proportion who gave a correct answer to 60% of the questions. RESULTS: Among the 488 students who completed the questionnaire, there was a male preponderance (55%). About three-quarters of the respondents (376, 77%) had a low sleep knowledge score. Age, year of study, and awareness about sleep medicine were the predictors of sleep knowledge. CONCLUSION: A significant proportion of the medical students had poor sleep knowledge scores. There is a need to incorporate teaching sleep medicine in the curriculum of medical students early in their training.

Translation and validation of an epilepsy-screening questionnaire in three Nigerian languages.

OBJECTIVE: We describe the development, translation and validation of epilepsy-screening questionnaires in the three most popular Nigerian languages: Hausa, Igbo and Yoruba. METHODS: A 9-item epilepsy-screening questionnaire was developed by modifying previously validated English language questionnaires. Separate multilingual experts forward- and back-translated them to the three target languages. Translations were discussed with fieldworkers and community members for ethnolinguistic acceptability and comprehension. We used an unmatched affected-case versus unaffected-control design for the pilot study. Cases were people with epilepsy attending the tertiary hospitals where these languages are spoken. The controls were relatives of cases or people attending for other medical conditions. An affirmative response to any of the nine questions amounted to a positive screen for epilepsy. RESULTS: We recruited 153 (75 cases and 78 controls) people for the Hausa version, 106 (45 cases and 61 controls) for Igbo and 153 (66 cases and 87 controls) for the Yoruba. The sensitivity and specificity of the questionnaire were: Hausa (97.3% and 88.5%), Igbo (91.1% and 88.5%) and Yoruba (93.9% and 86.7%). The three versions reliably indicated epilepsy with positive predictive values of 85.9% (Hausa), 85.4% (Igbo) and 87.3% (Yoruba) and reliably excluded epilepsy with negative predictive values of 97.1% (Hausa), 93.1% (Igbo) and 95.1% (Yoruba). Positive likelihood ratios were all greater than one. CONCLUSIONS: Validated epilepsy screening questionnaires are now available for the three languages to be used for community-based epilepsy survey in Nigeria. The translation and validation process are discussed to facilitate usage and development for other languages in sub-Saharan Africa.

Targeted next-generation sequencing identifies novel variants in candidate genes for Parkinson's disease in Black South African and Nigerian patients.

BACKGROUND: The prevalence of Parkinson's disease (PD) is increasing in sub-Saharan Africa, but little is known about the genetics of PD in these populations. Due to their unique ancestry and diversity, sub-Saharan African populations have the potential to reveal novel insights into the pathobiology of PD. In this study, we aimed to characterise the genetic variation in known and novel PD genes in a group of Black South African and Nigerian patients. METHODS: We recruited 33 Black South African and 14 Nigerian PD patients, and screened them for sequence variants in 751 genes using an Ion AmpliSeq™ Neurological Research panel. We used bcftools to filter variants and annovar software for the annotation. Rare variants were prioritised using MetaLR and MetaSVM prediction scores. The effect of a variant on ATP13A2's protein structure was investigated by molecular modelling. RESULTS: We identified 14,655 rare variants with a minor allele frequency ≤ 0.01, which included 2448 missense variants. Notably, no common pathogenic mutations were identified in these patients. Also, none of the known PD-associated mutations were found highlighting the need for more studies in African populations. Altogether, 54 rare variants in 42 genes were considered deleterious and were prioritized, based on MetaLR and MetaSVM scores, for follow-up studies. Protein modelling showed that the S1004R variant in ATP13A2 possibly alters the conformation of the protein. CONCLUSIONS: We identified several rare variants predicted to be deleterious in sub-Saharan Africa PD patients; however, further studies are required to determine the biological effects of these variants and their possible role in PD. Studies such as these are important to elucidate the genetic aetiology of this disorder in patients of African ancestry.

The Nigeria Parkinson Disease Registry: Process, Profile, and Prospects of a Collaborative Project.

BACKGROUND: Clinical disease registries are useful for quality improvement in care, benchmarking standards, and facilitating research. Collaborative networks established thence can enhance national and international studies by generating more robust samples and credible data and promote knowledge sharing and capacity building. This report describes the methodology, baseline data, and prospects of the Nigeria Parkinson Disease Registry. METHODS: This national registry was established in November 2016. Ethics approval was obtained for all sites. Basic anonymized data for consecutive cases fulfilling the United Kingdom Parkinson's Disease Brain Bank criteria (except the exclusion criterion of affected family members) are registered by participating neurologists via a secure registry website (www.parkinsonnigeria.com) using a minimal common data capture format. RESULTS: The registry had captured 578 participants from 5 of 6 geopolitical zones in Nigeria by July 2019 (72.5% men). Mean age at onset was 60.3 ± 10.7 years; median disease duration (interquartile range) was 36 months (18-60.5 months). Young-onset disease (<50 years) represented 15.2%. A family history was documented in 4.5% and 7.8% with age at onset <50 and ≥ 50, respectively. The most frequent initial symptom was tremor (45.3%). At inclusion, 93.4% were on treatment (54.5% on levodopa monotherapy). Per-capita direct cost for the registry was $3.37. CONCLUSIONS: This is the first published national Parkinson's disease registry in sub-Saharan Africa. The registry will serve as a platform for development of multipronged evidence-based policies and initiatives to improve quality of care of Parkinson's disease and research engagement in Nigeria. © 2020 International Parkinson and Movement Disorder Society.

Differential Impact of Risk Factors on Stroke Occurrence Among Men Versus Women in West Africa.

Background and Purpose- The interplay between sex and the dominant risk factors for stroke occurrence in sub-Saharan Africa has not been clearly delineated. We compared the effect sizes of risk factors of stroke by sex among West Africans. Methods- SIREN study (Stroke Investigative Research and Educational Networks) is a case-control study conducted at 15 sites in Ghana and Nigeria. Cases were adults aged >18 years with computerized tomography/magnetic resonance imaging confirmed stroke, and controls were age- and sex-matched stroke-free adults. Comprehensive evaluation for vascular, lifestyle, and psychosocial factors was performed using validated tools. We used conditional logistic regression to estimate odds ratios and reported risk factor specific and composite population attributable risks with 95% CIs. Results- Of the 2118 stroke cases, 1193 (56.3%) were males. The mean±SD age of males was 58.1±13.2 versus 60.15±14.53 years among females. Shared modifiable risk factors for stroke with adjusted odds ratios (95% CI) among females versus males, respectively, were hypertension [29.95 (12.49-71.77) versus 16.1 0(9.19-28.19)], dyslipidemia [2.08 (1.42-3.06) versus 1.83 (1.29-2.59)], diabetes mellitus [3.18 (2.11-4.78) versus 2.19 (1.53-3.15)], stress [2.34 (1.48-3.67) versus 1.61 (1.07-2.43)], and low consumption of green leafy vegetables [2.92 (1.89-4.50) versus 2.00 (1.33-3.00)]. However, salt intake and income were significantly different between males and females. Six modifiable factors had a combined population attributable risk of 99.1% (98.3%-99.6%) among females with 9 factors accounting for 97.2% (94.9%-98.7%) among males. Hemorrhagic stroke was more common among males (36.0%) than among females (27.6%), but stroke was less severe among males than females. Conclusions- Overall, risk factors for stroke occurrence are commonly shared by both sexes in West Africa favoring concerted interventions for stroke prevention in the region.

Sonographic Evaluation of Endothelial Function in Brachial Arteries of Adult Stroke Patients.

OBJECTIVES: Brachial artery flow-mediated dilatation on sonography is used to evaluate endothelial dysfunction, which is a key event in the development of atherosclerosis and predates structural atherosclerotic lesions by many years. Atherosclerosis has been implicated in the pathophysiologic mechanisms of ischemic stroke. The aim of this study was to determine the association between brachial flow-mediated dilatation, the presence of cardiovascular risk factors, and acute stroke. METHODS: We evaluated right brachial arteries of 150 participants (50 stroke patients, 50 patients with cardiovascular risk factors, and 50 healthy control individuals) with B-mode sonography before and 5 minutes after sphygmomanometer cuff application to their forearms. Analysis of variance for multiple comparisons was used between each group. RESULTS: Mean ages of the stroke, risk factor, and control groups ± SD were 57.5 ± 14.8, 52.4 ± 16.0, and 56.1 ± 14.9 years, respectively (P = .235). Flow-mediated dilatation rates were 4.37% ± 1.50%, 5.62% ± 1.23%, and 10.33% ± 1.96% in the stroke, risk factor, and control groups (P ≤ .001). Dilatation was 3.79% ± 0.92% in ischemic stroke compared with 6.02% ± 1.62% in intracerebral hemorrhage (P < .001), but there was no significant difference in dilatation between ischemic stroke subtypes according to the Trial of ORG 10172 in Acute Stroke Treatment classification (P = .301). CONCLUSIONS: Brachial flow-mediated dilatation was significantly lower in patients with acute stroke compared with controls matched for vascular risk factors and healthy controls. Decreased vascular endothelial function in stroke patients was particularly related to cerebral infarction compared with intracerebral hemorrhage. Brachial flow-mediated dilatation did not differentiate ischemic stroke subtypes by the Trial of ORG 10172 in Acute Stroke Treatment classification. Flow-mediated dilatation was therefore found to be a marker of cardiovascular risk and a probable reactant in the acute phase of stroke.

Development and Reliability of a User-Friendly Multicenter Phenotyping Application for Hemorrhagic and Ischemic Stroke.

BACKGROUND: Annotation and Image Markup on ClearCanvas Enriched Stroke-phenotyping Software (ACCESS) is a novel stand-alone computer software application that allows the creation of simple standardized annotations for reporting brain images of all stroke types. We developed the ACCESS application and determined its inter-rater and intra-rater reliability in the Stroke Investigative Research and Educational Network (SIREN) study to assess its suitability for multicenter studies. METHODS: One hundred randomly selected stroke imaging reports from 5 SIREN sites were re-evaluated by 4 trained independent raters to determine the inter-rater reliability of the ACCESS (version 12.0) software for stroke phenotyping. To determine intra-rater reliability, 6 raters reviewed the same cases previously reported by them after a month of interval. Ischemic stroke was classified using the Oxfordshire Community Stroke Project (OCSP), Trial of Org 10172 in Acute Stroke Treatment (TOAST), and Atherosclerosis, Small-vessel disease, Cardiac source, Other cause (ASCO) protocols, while hemorrhagic stroke was classified using the Structural lesion, Medication, Amyloid angiopathy, Systemic disease, Hypertensive angiopathy and Undetermined (SMASH-U) protocol in ACCESS. Agreement among raters was measured with Cohen's kappa statistics. RESULTS: For primary stroke type, inter-rater agreement was .98 (95% confidence interval [CI], .94-1.00), while intra-rater agreement was 1.00 (95% CI, 1.00). For OCSP subtypes, inter-rater agreement was .97 (95% CI, .92-1.00) for the partial anterior circulation infarcts, .92 (95% CI, .76-1.00) for the total anterior circulation infarcts, and excellent for both lacunar infarcts and posterior circulation infarcts. Intra-rater agreement was .97 (.90-1.00), while inter-rater agreement was .93 (95% CI, .84-1.00) for TOAST subtypes. Inter-rater agreement ranged between .78 (cardioembolic) and .91 (large artery atherosclerotic) for ASCO subtypes and was .80 (95% CI, .56-1.00) for SMASH-U subtypes. CONCLUSION: The ACCESS application facilitates a concordant and reproducible classification of stroke subtypes by multiple investigators, making it suitable for clinical use and multicenter research.

Effects of seizure severity and seizure freedom on the health-related quality of life of an African population of people with epilepsy.

PURPOSE: This study aimed at determining the effects of seizure severity and seizure freedom on health-related quality of life (HRQOL) of people with epilepsy (PWE) in the presence of perceived stigma in a sub-Saharan African culture. METHODS: Health-related quality of life was assessed using QOLIE-31 in 93 consecutive adults (56 males and 37 females) with epilepsy. They were stratified into seizure-free, low-moderate seizure severity, and high seizure severity groups based on the seizure type and the number of seizures in the previous 6months. Other illness variables and sociodemographic variables were also obtained. A 3-item perceived stigma scale was administered. A modified QOLIE-31 (excluding the epilepsy-specific items) was given to 102 age- and sex-matched healthy controls. RESULTS: There was moderate negative correlation between seizure severity and mean total HRQOL score as well as scores on the Seizure Worry (p=.000), Overall Quality of Life (p=.000), and Social Function (p=.001) subscales of QOLIE-31. Overall, the healthy control subjects had a higher mean HRQOL score compared with the PWE put together (71.0+11.1 vs 64.2±13.6, p=.001). However, there was no difference in the mean HRQOL score between the seizure-free individuals and the healthy controls (p=.270). Seizure severity was associated with HRQOL independent of perceived stigma on a multiple regression analysis. CONCLUSION: This study provides evidence that seizure severity relates to health-related quality of life in an inverse, graded manner and independent of perceived stigma. Seizure-free people with epilepsy can have quality of life comparable with healthy individuals.

Serum reference intervals of micronutrients, vitamins, and interleukins among healthy adults in South-Western Nigeria.

Objectives: Clinical decision making depends mostly on appropriate application of numerical pathology reports from laboratory results, interpreted by comparison with reference intervals. We determined serum reference intervals of micronutrients, vitamins, and detectable interleukins among healthy adults in South-Western Nigeria. Design and methods: This prospective study used a priori selection approach in blood-donors. They were screened for conditions that could elicit cytokine production.Serum micronutrients were assayed using Atomic Absorption Spectrophotometry; interleukins and vitamins by high Performance Liquid Chromatography. The reference intervals (RIs) were estimated at 2.5th percentile and 97.5th percentile. Results: One hundred and eighteen (118) apparently healthy subjects, aged 18-56 years; 113 (95.8%) being 18-44years, and 5 (4.2%): 45-56 years; mostly males, 13 (11.02%) females, all Africans of Yoruba ethnicity.Estimated reference limits were: Zinc: 9.49-20.54 µmol/L, Selenium: 0.50-1.11 µmol/L, Copper: 13.86-27.97 µmol/L, Iron: 14.19-32.07 µmol/L, Manganese: 6.24-16.37 nmol/L; Magnesium: 0.78-1.62 mmol/L.Vitamins: A-1.08-2.39 µmol/L; D: 59.89-164.42 µmol/L; E: 7.13-19.45 µmol/L; K: 0.16-0.42 nmol/L; B1: 74.09-201.56 nmol/L; B6: 0.12-0.29 nmol/L; B12: 155.55-407.96 pmol/L; C: 47.74-112.99 µmol/L.Detected interleukins (IL-1 to IL-18): IL-1: 0.58-1.24 ng/L, IL-2: 0.09-0.18 ng/L, IL-3: 0.39-0.89 ng/L, IL-4: 0.27-0.58 ng/L, ….to IL-18: 0.74-1.56 ng/L. Conclusions: The RI derived from this study for serum micronutrient, vitamin and interleukin concentrations are the first published for our population. They are in general agreement with those published from other geographical climes but there are differences at the lower and upper limits of the RI. The study reinforces the importance of deriving RI for the population that a clinical laboratory will serve.

MAPT allele and haplotype frequencies in Nigerian Africans: Population distribution and association with Parkinson's disease risk and age at onset.

INTRODUCTION: The association between MAPT and PD risk may be subject to ethnic variability even within populations of similar geographical origin. Data on MAPT haplotype frequencies, and its association with PD risk in black Africans are lacking. We aimed to determine the frequencies of MAPT haplotypes and their role as risk factors for PD and age at onset in Nigerians. METHODS: The haplotype and genotype frequencies of MAPT rs1052553 were analysed in 907 individuals with PD and 1022 age-matched healthy controls from the Nigeria Parkinson's Disease Research network cohort. Clinical data related to PD included age at study, age at onset (AAO), and disease duration. RESULTS: The frequency of the H1 haplotype was 98.7% in PD, and 99.1% in controls (p = 0.19). The H2 haplotype was present in - 1.3% of PD and 0.9% of controls (p = 0.24). The most frequent MAPT genotype was H1H1 (PD - 97.5%, controls - 98.2%). The H1 haplotype was not associated with PD risk after accounting for gender and AAO (Odds ratio for H1/H1 vs H1/H2 and H2/H2: 0.68 (95% CI:0.39-1.28); p = 0.23). CONCLUSIONS: Our findings support previous studies that report a low frequency of the MAPT H2 haplotype in black ancestry Africans but document its occurrence in Nigerians. The MAPT H1 haplotype was not associated with an increased risk or age at onset of PD in this cohort.

MAPT allele and haplotype frequencies in Nigerian Africans: population distribution and association with Parkinson's disease risk and age at onset.

Background: The microtubule-associated protein tau ( MAPT ) gene is critical because of its putative role in the causal pathway of neurodegenerative diseases including Parkinson's disease (PD). However, there is a lack of clarity regarding the link between the main H1 haplotype and risk of PD. Inconsistencies in reported association may be driven by genetic variability in the populations studied to date. Data on MAPT haplotype frequencies in the general population and association studies exploring the role of MAPT haplotypes in conferring PD risk in black Africans are lacking. Objectives: To determine the frequencies of MAPT haplotypes and explore the role of the H1 haplotype as a risk factor for PD risk and age at onset in Nigerian Africans. Methods: The haplotype and genotype frequencies of MAPT rs1052553 were analysed using PCR-based KASP™ in 907 individuals with PD and 1,022 age-matched neurologically normal controls from the Nigeria Parkinson's Disease Research (NPDR) network cohort. Clinical data related to PD included age at study, age at onset, and disease duration. Results: The frequency of the main MAPT H1 haplotype in this cohort was 98.7% in individuals with PD, and 99.1% in healthy controls (p=0.19). The H2 haplotype was present in 41/1929 (2.1%) of the cohort (PD - 1.3%; Controls - 0.9%; p=0.24). The most frequent MAPT genotype was H1H1 (PD - 97.5%, controls - 98.2%). The H1 haplotype was not associated with PD risk after accounting for gender and age at onset (Odds ratio for H1/H1 vs H1/H2 and H2/H2: 0.68 (95% CI:0.39-1.28); p=0.23). Conclusions: Our findings support previous studies that report a low frequency of the MAPT H2 haplotype in black ancestry Africans, but document its occurrence in the Nigerian population (2.1%). In this cohort of black Africans with PD, the MAPT H1 haplotype was not associated with an increased risk or age at onset of PD.

Identification of genetic risk loci and causal insights associated with Parkinson's disease in African and African admixed populations: a genome-wide association study.

BACKGROUND: An understanding of the genetic mechanisms underlying diseases in ancestrally diverse populations is an important step towards development of targeted treatments. Research in African and African admixed populations can enable mapping of complex traits, because of their genetic diversity, extensive population substructure, and distinct linkage disequilibrium patterns. We aimed to do a comprehensive genome-wide assessment in African and African admixed individuals to better understand the genetic architecture of Parkinson's disease in these underserved populations. METHODS: We performed a genome-wide association study (GWAS) in people of African and African admixed ancestry with and without Parkinson's disease. Individuals were included from several cohorts that were available as a part of the Global Parkinson's Genetics Program, the International Parkinson's Disease Genomics Consortium Africa, and 23andMe. A diagnosis of Parkinson's disease was confirmed clinically by a movement disorder specialist for every individual in each cohort, except for 23andMe, in which it was self-reported based on clinical diagnosis. We characterised ancestry-specific risk, differential haplotype structure and admixture, coding and structural genetic variation, and enzymatic activity. FINDINGS: We included 197 918 individuals (1488 cases and 196 430 controls) in our genome-wide analysis. We identified a novel common risk factor for Parkinson's disease (overall meta-analysis odds ratio for risk of Parkinson's disease 1·58 [95% CI 1·37-1·80], p=2·397 × 10-14) and age at onset at the GBA1 locus, rs3115534-G (age at onset ß=-2·00 [SE=0·57], p=0·0005, for African ancestry; and ß=-4·15 [0·58], p=0·015, for African admixed ancestry), which was rare in non-African or non-African admixed populations. Downstream short-read and long-read whole-genome sequencing analyses did not reveal any coding or structural variant underlying the GWAS signal. The identified signal seems to be associated with decreased glucocerebrosidase activity. INTERPRETATION: Our study identified a novel genetic risk factor in GBA1 in people of African ancestry, which has not been seen in European populations, and it could be a major mechanistic basis of Parkinson's disease in African populations. This population-specific variant exerts substantial risk on Parkinson's disease as compared with common variation identified through GWAS and it was found to be present in 39% of the cases assessed in this study. This finding highlights the importance of understanding ancestry-specific genetic risk in complex diseases, a particularly crucial point as the Parkinson's disease field moves towards targeted treatments in clinical trials. The distinctive genetics of African populations highlights the need for equitable inclusion of ancestrally diverse groups in future trials, which will be a valuable step towards gaining insights into novel genetic determinants underlying the causes of Parkinson's disease. This finding opens new avenues towards RNA-based and other therapeutic strategies aimed at reducing lifetime risk of Parkinson's disease. FUNDING: The Global Parkinson's Genetics Program, which is funded by the Aligning Science Across Parkinson's initiative, and The Michael J Fox Foundation for Parkinson's Research.

Genome-wide Association Identifies Novel Etiological Insights Associated with Parkinson's Disease in African and African Admixed Populations.

Background: Understanding the genetic mechanisms underlying diseases in ancestrally diverse populations is a critical step towards the realization of the global application of precision medicine. The African and African admixed populations enable mapping of complex traits given their greater levels of genetic diversity, extensive population substructure, and distinct linkage disequilibrium patterns. Methods: Here we perform a comprehensive genome-wide assessment of Parkinson's disease (PD) in 197,918 individuals (1,488 cases; 196,430 controls) of African and African admixed ancestry, characterizing population-specific risk, differential haplotype structure and admixture, coding and structural genetic variation and polygenic risk profiling. Findings: We identified a novel common risk factor for PD and age at onset at the GBA1 locus (risk, rs3115534-G; OR=1.58, 95% CI = 1.37 - 1.80, P=2.397E-14; age at onset, BETA =-2.004, SE =0.57, P = 0.0005), that was found to be rare in non-African/African admixed populations. Downstream short- and long-read whole genome sequencing analyses did not reveal any coding or structural variant underlying the GWAS signal. However, we identified that this signal mediates PD risk via expression quantitative trait locus (eQTL) mechanisms. While previously identified GBA1 associated disease risk variants are coding mutations, here we suggest a novel functional mechanism consistent with a trend in decreasing glucocerebrosidase activity levels. Given the high population frequency of the underlying signal and the phenotypic characteristics of the homozygous carriers, we hypothesize that this variant may not cause Gaucher disease. Additionally, the prevalence of Gaucher's disease in Africa is low. Interpretation: The present study identifies a novel African-ancestry genetic risk factor in GBA1 as a major mechanistic basis of PD in the African and African admixed populations. This striking result contrasts to previous work in Northern European populations, both in terms of mechanism and attributable risk. This finding highlights the importance of understanding population-specific genetic risk in complex diseases, a particularly crucial point as the field moves toward precision medicine in PD clinical trials and while recognizing the need for equitable inclusion of ancestrally diverse groups in such trials. Given the distinctive genetics of these underrepresented populations, their inclusion represents a valuable step towards insights into novel genetic determinants underlying PD etiology. This opens new avenues towards RNA-based and other therapeutic strategies aimed at reducing lifetime risk. Evidence Before this Study: Our current understanding of Parkinson's disease (PD) is disproportionately based on studying populations of European ancestry, leading to a significant gap in our knowledge about the genetics, clinical characteristics, and pathophysiology in underrepresented populations. This is particularly notable in individuals of African and African admixed ancestries. Over the last two decades, we have witnessed a revolution in the research area of complex genetic diseases. In the PD field, large-scale genome-wide association studies in the European, Asian, and Latin American populations have identified multiple risk loci associated with disease. These include 78 loci and 90 independent signals associated with PD risk in the European population, nine replicated loci and two novel population-specific signals in the Asian population, and a total of 11 novel loci recently nominated through multi-ancestry GWAS efforts.Nevertheless, the African and African admixed populations remain completely unexplored in the context of PD genetics. Added Value of this Study: To address the lack of diversity in our research field, this study aimed to conduct the first genome-wide assessment of PD genetics in the African and African admixed populations. Here, we identified a genetic risk factor linked to PD etiology, dissected African-specific differences in risk and age at onset, characterized known genetic risk factors, and highlighted the utility of the African and African admixed risk haplotype substructure for future fine-mapping efforts. We identified a novel disease mechanism via expression changes consistent with decreased GBA1 activity levels. Future large scale single cell expression studies should investigate the neuronal populations in which expression differences are most prominent. This novel mechanism may hold promise for future efficient RNA-based therapeutic strategies such as antisense oligonucleotides or short interfering RNAs aimed at preventing and decreasing disease risk. We envisage that these data generated under the umbrella of the Global Parkinson's Genetics Program (GP2) will shed light on the molecular mechanisms involved in the disease process and might pave the way for future clinical trials and therapeutic interventions. This work represents a valuable resource in an underserved population, supporting pioneering research within GP2 and beyond. Deciphering causal and genetic risk factors in all these ancestries will help determine whether interventions, potential targets for disease modifying treatment, and prevention strategies that are being studied in the European populations are relevant to the African and African admixed populations. Implications of all the Available Evidence: We nominate a novel signal impacting GBA1 as the major genetic risk factor for PD in the African and African admixed populations. The present study could inform future GBA1 clinical trials, improving patient stratification. In this regard, genetic testing can help to design trials likely to provide meaningful and actionable answers. It is our hope that these findings may ultimately have clinical utility for this underrepresented population.

Outcome of Delayed Administration of Alteplase in a Resource-Poor Area: A Case Report.

An acute ischemic stroke, though carrying the risk of debilitating complications, is a preventable and treatable disease. Thrombolysis and endovascular thrombectomy are important components of its management. However, various challenges in resource-poor countries like Nigeria and other developing nations pose a great limitation in the timely intervention of ischemic stroke treatment. The challenges include late presentation, poor awareness of stroke symptoms even among health care workers, poor ambulance service/transportation network, intra-hospital delay, particularly in neuroimaging, and the unavailability of tissue plasminogen activator (alteplase/tenecteplase). We report a 32-year-old African man with an antecedent history of suspected migraine headaches with aura and a family history of hypertension and stroke, admitted 7½ hours after onset of stroke symptoms, scoring 13 on the National Institutes of Health Stroke Scale (NIHSS) with Medical Research Council (MRC) muscle power grades 1 and 3 on the right upper and lower extremities, respectively. Urgent non-contrast brain CT revealed only a hyperdense sign in the left middle cerebral artery (MCA). Intravenous tissue plasminogen activator (tPA) was administered at a lower dose of 0.6 mg/kg, 15½ hours after symptom onset, and a CT angiogram done 24 hours post-thrombolysis showed partial recanalization of the M1 segment of the MCA and intermediate collateral supply (Alberta stroke program early CT {ASPECT} score: 6). By the third day of admission, he had made a significant clinical improvement and was discharged home able to walk unsupported on the fourth day.

Serum Interleukin-6 and Weight Loss in Antiretroviral-naïve and Antiretroviral-treated Patients with HIV/AIDS: Relationships and Predictors.

BACKGROUND: Cachexia is usually associated with elevated serum interleukin-6 (IL.6) as it stimulates the breakdown of muscle proteins and promotes wasting. OBJECTIVE: A case-control study to evaluate the relationship between weight loss, facial fat loss, and IL-6 in antiretroviral-naïve and treated participants living with HIV/AIDS. METHODS: IL-6 was assayed by High performance liquid chromatography (HPLC) in 97 in consecutive newly diagnosed antiretroviral-naive (ART-naïve) people living with HIV/AIDS (age ≥18 years); and 118 consecutive, age-matched participants currently on Highly Active Antiretroviral Therapy (HAART), using age as a criterion. In the treated group, 78 (66.7%) subjects were on zidovudine, lamivudine with nevirapine (Z+L+N); 27(23.1%) on tenofovir, lamivudine with emtricitabine (T+L+E); 5(4.3%) on zidovudine, lamivudine with emtricitabine (Z+L+E); 4(3.4%) on zidovudine, lamivudine with tenofovir (Z+L+T); 2(1.7%) on lamivudine, tenofovir with nevirapine (L+T+N); 1(0.9%) on tenofovir, zidovudine, emtricitabine (Z+T+E). RESULTS: A total of 215 participants: 97 ART-naive and 118 HAART-treated, age-matched subjects (40.3±9.6 versus 42.7±10.20years, p=0.08). The mean IL-6 was significantly higher in naïve than treated (0.69±0.04 versus 0.66±0.04 pg/ml, p =0.002). In all, 73 subjects experienced weight loss, 56(76.7%) naive, 17(23.3%) treated, p <0.0001, with significantly higher IL-6 in those with weight loss (0.69±0.05 versus 0.67±0.05pg/ml, p= 0.047). Fifty-eight (27.0%) subjects experienced facial fat loss, 49 (84.5%) naïve, and 9 (15.5%) treated, p <0.0001, with significantly higher IL-6 in those with facial fat loss (0.7 ± 0.05 versus 0.67±0.05pg/ml, p= 0.0001). Negative correlation exists between IL-6 and CD4+ count (r=-0.141, p=0.041). In logistic regression, independent predictors of weight loss include: IL-6 (Adjusted Odds Ratio, aOR 1.3, 95%CI 0·1-2·6, p=0.047); HIV duration (aOR 11.6, p <0.0001); AIDS-defining illness (aOR 3.5, p <0.0001); CD4+ count (aOR 3.2, p=0.004); HAART status (aOR 2.7, p<0.0001). CONCLUSION: HIV infection is associated with elevation of serum interleukin-6, which likely contributes to weight and facial fat loss among the treatment-naïve participants; while HAART is associated with suppressed IL-6 levels, thereby ameliorating weight and facial fat loss. Inverse relationship exists between serum IL-6 and CD4+ count; serum IL-6 could differentiate between mild- to moderate and severe immunosuppressive states.

Secondhand smoke exposure is independently associated with stroke among non-smoking adults in West Africa.

BACKGROUND: Stroke is a leading cause of disability and mortality worldwide, but little is known about the contribution of secondhand smoke exposure (SHSE) to stroke epidemiology among indigenous Africans. OBJECTIVE: To evaluate the association of SHSE with stroke among indigenous Africans. METHODS: We analyzed the relationship of SHSE with stroke among 2990 case-control pairs of adults who had never smoked (identified in the SIREN study) using conditional logistic regression at a two-sided P < 0.05. RESULTS: Multivariable-adjusted odds ratio and 95% confidence interval; 1.25 (1.04, 1.50; P = 0.02) revealed SHSE was positively associated with stroke independent of stroke subtypes. CONCLUSION: Culturally relevant primary prevention strategies targeted at SHSE might be promising in preventing stroke among Africans.

APOE E4 is associated with impaired self-declared cognition but not disease risk or age of onset in Nigerians with Parkinson's disease.

The relationship between APOE polymorphisms and Parkinson's disease (PD) in black Africans has not been previously investigated. We evaluated the association between APOE polymorphic variability and self-declared cognition in 1100 Nigerians with PD and 1097 age-matched healthy controls. Cognition in PD was assessed using the single item cognition question (item 1.1) of the MDS-UPDRS. APOE genotype and allele frequencies did not differ between PD and controls (p > 0.05). No allelic or genotypic association was observed between APOE and age at onset of PD. In PD, APOE ε4/ε4 conferred a two-fold risk of cognitive impairment compared to one or no ε4 (HR: 2.09 (95% CI: 1.13-3.89; p = 0.02)), while APOE ε2 was associated with modest protection against cognitive impairment (HR: 0.41 (95% CI 0.19-0.99, p = 0.02)). Of 773 PD with motor phenotype and APOE characterized, tremor-dominant (TD) phenotype predominated significantly in ε2 carriers (87/135, 64.4%) compared to 22.2% in persons with postural instability/gait difficulty (PIGD) (30/135) and 13.3% in indeterminate (ID) (18/135, 13.3%) (p = 0.037). Although the frequency of the TD phenotype was highest in homozygous ε2 carriers (85.7%), the distribution of motor phenotypes across the six genotypes did not differ significantly (p = 0.18). Altogether, our findings support previous studies in other ethnicities, implying a role for APOE ε4 and ε2 as risk and protective factors, respectively, for cognitive impairment in PD.

Carotid and Vertebral Atherosclerosis in West African Stroke Patients: Findings from the Stroke Investigative Research and Education Network.

Background: We evaluated the characteristics of carotid and vertebral atherosclerosis in indigenous West Africans with stroke. Methodology: Of the 3778stroke patients recruited between 01/2014 and 08/2017, 1070 (28.3%) received carotid and vertebral artery evaluation with B-mode Ultrasound. Carotid and vertebral intima-media thickness (IMT) using multiple site technique were measured bilaterally and plaque frequency was determined. Descriptive and comparative analyses between stroke types and vessels were carried out. Results: There were 809 (75.6%) patients with ischemic stroke. The prevalence of intima-media thickening in the study population was 84.0% (898/1070) [95% CI: 81.7-86.1], being higher in the ischemic stroke (688/809, 85.0%) [95% CI: 82.4-87.3] than in the hemorrhagic stroke group (211/261, 80.8%) [95% CI: 75.6-85.2]. Overall prevalence of plaques which was 26.1% [95% CI: 23.5-28.8], was found also to be higher in ischemic than hemorrhagic stroke (29.8%[95% CI: 26.7-33.0] vs. 14.6% [95% CI: 10.8-19.4], p < 0.05). The mean IMT (carotids: 2.01+1.33 mm; vertebrals: 0.96+0.54mm, p<0.001) and prevalence of plaques (carotids: 8.8%; vertebrals: 1.7%,p<0.001) were higher in carotid than vertebral arteries. Age, hypertension, level of formal education, history of smoking, average monthly income, and family histories of hypertension and stroke were associated with intima-media thickening in the carotids (all p< 0.05) in the ischemic stroke patients while family history of hypertension, diabetes mellitus, and level of formal education were independently associated with intima-media thickening in the carotids (all p< 0.05) in the hemorrhagic stroke patients. No CVRF showed an independent association with the presence of plaque in the carotid and vertebral arteries both stroke types. Conclusions: One off our stroke patients in our cohort had atherosclerotic plaques, with ischemic patients being twice as likely to have this burden compared to hemorrhagic patients, and carotid atherosclerosis being five times as frequent as vertebral atherosclerosis.

Sleep medicine in Africa: past, present, and future.

NONE: Interest in sleep and sleep disorders in Africa dates back thousands of years, influenced by various cultural and religious beliefs. However, the practice of sleep medicine as a specialty has been inadequate compared to other regions of the world. The objective of this study was to explore the current status of sleep medicine in Africa vis-à-vis education, professional societies, and facilities, and to identify challenges of the specialty in the region. A literature search of major electronic databases (PubMed, Google Scholar) was done. This revealed that there is a high prevalence of sleep disorders in Africa and a significant association with epilepsy, human African trypanosomiasis, human immunodeficiency virus, and other diseases. There are 6 sleep societies in Africa located in 4 countries. Forty-one sleep laboratories were identified located in 4 countries. The challenges hindering development of sleep medicine in Africa include lack of awareness, poor funding, lack of facilities, and inadequate training.