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2021
Sarfo, F, Akpa O, Ovbiagele B, Akpalu A, Wahab K, Komolafe M, Obiako R, Owolabi L, Osaigbovo G, Jenkins C, Ogbole G, Fakunle A, Tiwari H, Arulogun O, Arnett D, Asowata O, Ogah O, Akinyemi R, Owolabi M.  2021.  Influence of age on links between major modifiable risk factors and stroke occurrence in West Africa, 2021/07/01. 428:117573. Abstract
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Akpa, OM, Okekunle AP, Ovbiagele B, Sarfo FS, Akinyemi RO, Akpalu A, Wahab KW, Komolafe M, Obiako R, Owolabi LF, Ogbole G, Fawale B, Fakunle A, Asaleye CM, Akisanya CO, Hamisu DA, Ogunjimi L, Adeoye A, Ogah O, Lackland D, Uvere EO, Faniyan MM, Asowata OJ, Adeleye O, Aridegbe M, Olunuga T, Yahaya IS, Olaleye A, Calys-Tagoe B, Owolabi MO.  2021.  Factors associated with hypertension among stroke-free indigenous Africans: Findings from the SIREN study, 2021. Journal of Clinical Hypertension. 23(4) Abstract

Hypertension is one of the most important risk factors for stroke and cardiovascular diseases (CVD) globally. Understanding risk factors for hypertension among individuals with matching characteristics with stroke patients may inform primordial/primary prevention of hypertension and stroke among them. This study identified the risk factors for hypertension among community-dwelling stroke-free population in Ghana and Nigeria. Data for 4267 community-dwelling stroke-free controls subjects in the Stroke Investigative Research and Education Network (SIREN) study in Nigeria and Ghana were used. Participants were comprehensively assessed for sociodemographic, lifestyle and metabolic factors using standard methods. Hypertension was defined as a previous diagnosis by a health professional or use of an anti-hypertensive drug or mean systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg. Logistic regression analysis was used to estimate adjusted odds ratios (aOR) of hypertension and their 95% confidence intervals (CI) at p <.05. Overall, 56.7% of the participants were hypertensive with a higher proportion among respondents aged ≥60 years (53.0%). Factors including physical inactivity (aOR: 9.09; 95% CI: 4.03 to 20.53, p <.0001), diabetes (aOR: 2.70; CI: 1.91 to 3.82, p <.0001), being ≥60 years (aOR: 2.22; 95% CI: 1.78 to 2.77, p <.0001), and family history of CVD (aOR 2.02; CI: 1.59 to 2.56, p <.0001) were associated with increased aOR of hypertension. Lifestyle factors were associated with hypertension in the current population of community-dwelling stroke-free controls in west Africa. Community-oriented interventions to address sedentary lifestyles may benefit this population and reduce/prevent hypertension and stroke among them.

Sarfo, FS, Akpa O, Ovbiagele B, Akpalu A, Wahab K, Komolafe M, Obiako R, Owolabi L, Osaigbovo GO, Jenkins C, Ogbole G, Fakunle A, Tiwari HK, Arulogun O, Arnett DK, Asowata O, Ogah O, Akinyemi RO, Owolabi MO.  2021.  Influence of age on links between major modifiable risk factors and stroke occurrence in West Africa, 2021. Journal of the Neurological Sciences. 428 Abstract

Background The burden of stroke in Africa is high. Understanding how age associates with major modifiable stroke risk factors could inform tailored demographic stroke prevention strategies. Purpose To quantify the magnitude and direction of the effect sizes of key modifiable stroke risk factors according to three age groups: <50 years (young), 50–65 years (middle age) and > 65 years (elderly) in West Africa. Methods This was a case-control study involving 15 sites in Ghana and Nigeria. Cases included adults aged ≥18 years with CT/MRI scan-typed stroke. Controls were age-and gender-matched stroke-free adults. Detailed evaluations for vascular, lifestyle and psychosocial factors were performed. We estimated adjusted odds ratios (aOR) using conditional logistic regression and population attributable risk (PAR) with 95% Confidence Interval of vascular risk factors by age groups. Results Among 3553 stroke cases, 813 (22.9%) were young, 1441 (40.6%) were middle-aged and 1299 (36.6%) were elderly. Among the 5 co-shared risk factors, dyslipidemia with PAR and aOR (95%CI) of 62.20% (52.82–71.58) and 4.13 (2.64–6.46) was highest among the young age group; hypertension with PAR of 94.31% (91.82–96.80) and aOR of 28.93 (15.10–55.44) was highest among the middle-age group. Diabetes with PAR of 32.29%(27.52–37.05) and aOR of 3.49 (2.56–4.75); meat consumption with PAR of 42.34%(32.33–52.35) and aOR of 2.40 (1.76, 3.26); and non-consumption of green vegetables, PAR of 16.81%(12.02–21.60) and aOR of 2.23 (1.60–3.12) were highest among the elderly age group. However confidence intervals of risk estimates overlapped across age groups. Additionally, among the young age group cigarette smoking, psychosocial stress and cardiac disease were independently associated with stroke. Furthermore, education, stress, physical inactivity and salt intake were associated with stroke in the middle-age group while cardiac disease was associated with stroke in the elderly age group. Conclusion There is a differential influence of age on the associations of major risk factors with stroke in this West African cohort. Targeting modifiable factors predominant within an age group may be more effective as a stroke prevention strategy.

Akpa, O, Sarfo FS, Owolabi M, Akpalu A, Wahab K, Obiako R, Komolafe M, Owolabi L, Osaigbovo GO, Ogbole G, Tiwari HK, Jenkins C, Fakunle AG, Olowookere S, Uvere EO, Akinyemi J, Arulogun O, Akpalu J, Tito-Ilori MM, Asowata OJ, Ibinaiye P, Akisanya C, Oyinloye OI, Appiah L, Sunmonu T, Olowoyo P, Agunloye AM, Adeoye AM, Yaria J, Lackland DT, Arnett D, Laryea RY, Adigun TO, Okekunle AP, Calys-Tagoe B, Ogah OS, Ogunronbi M, Obiabo OY, Isah SY, Dambatta HA, Tagge R, Ogenyi O, Fawale B, Melikam CL, Onasanya A, Adeniyi S, Akinyemi R, Ovbiagele B.  2021.  A Novel Afrocentric Stroke Risk Assessment Score: Models from the Siren Study, 2021. Journal of Stroke and Cerebrovascular Diseases. 30(10) Abstract

Background: Stroke risk can be quantified using risk factors whose effect sizes vary by geography and race. No stroke risk assessment tool exists to estimate aggregate stroke risk for indigenous African. Objectives: To develop Afrocentric risk-scoring models for stroke occurrence. Materials and Methods: We evaluated 3533 radiologically confirmed West African stroke cases paired 1:1 with age-, and sex-matched stroke-free controls in the SIREN study. The 7,066 subjects were randomly split into a training and testing set at the ratio of 85:15. Conditional logistic regression models were constructed by including 17 putative factors linked to stroke occurrence using the training set. Significant risk factors were assigned constant and standardized statistical weights based on regression coefficients (β) to develop an additive risk scoring system on a scale of 0–100%. Using the testing set, Receiver Operating Characteristics (ROC) curves were constructed to obtain a total score to serve as cut-off to discriminate between cases and controls. We calculated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) at this cut-off. Results: For stroke occurrence, we identified 15 traditional vascular factors. Cohen's kappa for validity was maximal at a total risk score of 56% using both statistical weighting approaches to risk quantification and in both datasets. The risk score had a predictive accuracy of 76% (95%CI: 74–79%), sensitivity of 80.3%, specificity of 63.0%, PPV of 68.5% and NPV of 76.2% in the test dataset. For ischemic strokes, 12 risk factors had predictive accuracy of 78% (95%CI: 74–81%). For hemorrhagic strokes, 7 factors had a predictive accuracy of 79% (95%CI: 73–84%). Conclusions: The SIREN models quantify aggregate stroke risk in indigenous West Africans with good accuracy. Prospective studies are needed to validate this instrument for stroke prevention.

Komolafe, MA, Sanusi AA, Idowu AO, Balogun SA, Olorunmonteni OE, Adebowale AA, Fawale MB, Mosaku KS.  2021.  Sleep medicine in Africa: Past, present, and future, 2021. Journal of Clinical Sleep Medicine. 17(6) Abstract

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.

Watila, MM, Balarabe SA, Komolafe M, Igwe SC, Bimbo Fawale M, van Diessen E, Nyandaiti YW, Singh G, Winkler AS, Sander JW.  2021.  Translation and validation of an epilepsy-screening questionnaire in three Nigerian languages, 2021. Epilepsy and Behavior. 114 Abstract

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.

2020
Sarfo, FS, Ovbiagele B, Matthew OA, Akpalu A, Wahab K, Obiako R, Owolabi L, Asowata O, Ogbole G, Komolafe M, Akinyemi R, Owolabi M.  2020.  Antecedent febrile illness and occurrence of stroke in West Africa: The SIREN study, 2020. Journal of the Neurological Sciences. 418 Abstract

Background: Acute infections have been posited as potential precipitants or triggers of the occurrence of stroke among adults with traditional vascular risk factors. We evaluated associations between stroke occurrence and reported febrile illness within 4 weeks (potential antecedent infections) among West Africans. Methods: The Stroke Investigative Research and Educational Network (SIREN) is a multicenter, case-control study involving 15 sites in Ghana and Nigeria. Cases include adults aged ≥18 years with radiologically confirmed strokes. Controls were stroke-free adults matched with cased by age, gender and ethnicity. Detailed evaluations for vascular, lifestyle and psychosocial factors were performed. Participants were asked for evidence of any febrile illness within the past 4 weeks. We used conditional logistic regression to estimate adjusted odds ratios (aOR) with 95% Confidence Interval. Results: Among 3588 stroke cases recruited in Ghana and Nigeria between August 2014 and July 2018, 363 cases (10.1%) reported having a febrile illness within the 4 weeks prior to stroke occurrence. Having an antecedent infection was associated with stroke occurrence with an unadjusted OR of 1.19 (1.00–1.51) but aOR of 0.83 (0.59–1.17) upon adjusting for traditional vascular risk factors. Stress, aOR of 4.69 (2.59–8.50) and consumption of green vegetables 2.27 (1.35–2.85) were associated with antecedent febrile illness. Conclusion: 1 in 10 stroke cases reported antecedent history of febrile illness prior to occurrence of stroke but no independent association was observed in this study. Infectious exposures may be important triggers of cardiovascular events requiring further exploratory studies to better understand the role of this emerging risk factor.

Adebiyi, AM, Komolafe MA, Idowu AO, Omon HE, Ogunniyi A.  2020.  Cardiac autonomic neuropathy in adult epilepsy patients in a tertiary hospital in South-Western Nigeria, 2020. Nigerian journal of clinical practice. 23(10) Abstract

Background: Cardiac autonomic neuropathy (CAN) resulting from seizures has been implicated in sudden unexpected death in epilepsy in persons with epilepsy (PWE), however, there are no previous studies of CAN in PWE from Nigeria. Objectives: This study sought to determine the frequency and pattern of CAN in adult PWE in a tertiary hospital in South-western Nigeria and to determine the relationship between seizure variables and CAN. Methods: A cross-sectional study of 80 adult PWE and 80 matched controls aged between 18 and 60 years was carried out between March 2012 and June 2013 at the Obafemi Awolowo University Teaching Hospital Complex, Ile-Ife, Nigeria. Demographic and clinical data were obtained from all the study participants. Anxiety was excluded using the Hamilton Anxiety Scale. Those with conditions that could affect autonomic function, such as chronic renal failure, heart failure, Parkinson's disease, diabetes mellitus, anxiety, and psychiatric disorders and pregnant women were excluded. Five bedside cardiovascular reflex tests were performed on each subject after baseline heart rate and blood pressure (BP) had been recorded. Results: The mean age of onset of epilepsy was 19 ± 10 years, whereas the mean duration of epilepsy was 10 ± 8 years. The mean seizure frequency was 14 ± 30 per month (median three seizures per month). Of the 80 patients evaluated, 42 (52.5%) had CAN, whereas none of the controls had CAN. Majority (69%) of the PWE with CAN had purely parasympathetic dysfunction, whereas 3% had purely sympathetic dysfunction and 10% had combined autonomic dysfunction. The PWE in this study had significantly lower tilt ratios and diastolic BP change with Isometric Hand grip as well as significantly higher systolic BP change on standing than the controls. Patients who had more than four seizures per month had higher odds of CAN than those with less frequent seizures (odds ratio 0.275, P value 0.023). Also, patients who had received treatment for less than 10 years were found to have greater odds of CAN than those who had received treatment for a longer period (odds ratio 11.676, P value 0.046). Conclusion: CAN is common in adult PWE in South-Western Nigeria and the major predictors are short duration of treatment and frequent seizure episodes. Routine screening of these patients may help with early detection of autonomic dysfunction and provide an opportunity for intervention.

Osayande, E, Ayodele KP, Komolafe MA.  2020.  Development of a Robotic Hand Orthosis for Stroke Patient Rehabilitation, 2020. International journal of online and biomedical engineering. 16(3) Abstract

This study developed a robotic orthosis capable of detecting the intention of a wearer to move their fingers, thereafter augmenting their muscle force. This was with the aim of producing a device that can be used in post-stroke hand rehabilitation. The design of the orthosis was based on an existing design, which was modified using BLENDER release 2.78 and printed with ABS plastic. An actuator was mounted at the rear end of the orthosis, to provide actuation to perform full range flexion and extension motion for digits. Force sensors were embedded at the fingertips of the orthosis to detect minute finger movements. For severe cases where stroke survivors are incapable of little finger movements, the study employed a brain-computer interface to detect the intent to move. The robotic orthosis achieved an accuracy of 64.1% and 62% in detecting unclench and clench activities respectively and actuating the orthosis digits in response. The results revealed that the design presented here can help provide effective hand rehabilitation. The study concluded that the design incorporated with BCI systems is capable of performing hand rehabilitation in a clinical setting as it obtains some level of accuracy in detecting patient intent to move and actuating in response. This design is low cost, and hence will lessen the economic burden for stroke survivors in a poor-resource country.

Komolafe, MA, Olorunmoteni OE, Fehintola FO.  2020.  Effect of Health Education on Level of Awareness and Knowledge of Nigerian In-School adolescents on Stroke and Its Risk Factors, 2020. Journal of Stroke and Cerebrovascular Diseases. 29(5) Abstract

Background: Stroke education in adolescents has been established as an effective method of creating awareness about stroke, its warning signs and risk factors. It contributes to desired behavioural change in the adolescents as well as their parents. Thus, we aimed to determine the baseline knowledge of school attending adolescents about stroke and its risk factors as well as the effect of stroke education on their stroke awareness. Methods: This study employed a quasi-experimental study design and was conducted in secondary schools in Ile-Ife, Osun State, Nigeria. The schools were divided into intervention and control groups. We assessed the baseline knowledge of the students on stroke, its risk factors, warning signs, and ways of preventing it using a pre-tested structured questionnaire in both intervention and control groups. In the intervention group, health talks on stroke consisting of oral presentation and distribution of fliers were presented for 30 minutes in each selected school. Each school was visited 2 weeks after the health education intervention to assess their knowledge on stroke, its risk factors, and ways of preventing it. The control group was also visited after 2 weeks for a re-assessment of their stroke knowledge and the conduct of heath talk on other aspects of neurology such as sleep, epilepsy, etc. Results: A total of 1259 adolescents were studied with 661 in the intervention group and 598 in the control group. The mean age of the respondents was 13.56 ± 2.87 the intervention group and 13.38 ± 2.06 in the control group. There were higher mean scores on knowledge of stroke and its risk factors among the intervention group than seen in the control group after the stroke education. Conclusions: Stroke education is an effective way of creating and maintaining stroke awareness among school-attending adolescents.

Ojo, OO, Abubakar SA, Iwuozo EU, Nwazor EO, Ekenze OS, Farombi TH, Akinyemi RO, Williams UE, Bello AH, Wahab KW, Iyagba AM, Arigbodi O, Erameh CO, Komolafe MA, Fawale MB, Onwuegbuzie GA, Obiabo YO, Taiwo FT, Agu CE, Ekeh BC, Osaigbovo GO, Achoru CO, Arabambi B, Adeniji O, Nwani PO, Nwosu CM, Ademiluyi BA, Oyakhire SI, Nyandaiti Y, Rabiu M, Chapp-Jumbo EN, Balarabe SA, Otubogun FM, Obehighe EE, Kehinde AJ, Ani-Osheku I, Imarhiagbe FA, Dike FO, Adebowale AA, Agabi OP, Akpekpe JE, Ali MW, Odeniyi OA, Odiase FE, Abiodun OV, Olowoyo P, Osemwegie N, Oshinaike OO, Owolabi LF, Zubair YA, Rizig M, Okubadejo NU.  2020.  The Nigeria Parkinson Disease Registry: Process, Profile, and Prospects of a Collaborative Project, 2020. Movement Disorders. 35(8) Abstract

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.

Dekker, MCJ, Coulibaly T, Bardien S, Ross OA, Carr J, Komolafe M.  2020.  Parkinson's Disease Research on the African Continent: Obstacles and Opportunities, 2020. Frontiers in Neurology. 11 Abstract

The burden of Parkinson's disease (PD) is becoming increasingly important in the context of an aging African population. Although PD has been extensively investigated with respect to its environmental and genetic etiology in various populations across the globe, studies on the African continent remain limited. In this Perspective article, we review some of the obstacles that are limiting research and creating barriers for future studies. We summarize what research is being done in four sub-Saharan countries and what the key elements are that are needed to take research to the next level. We note that there is large variation in neurological and genetic research capacity across the continent, and many opportunities for unexplored areas in African PD research. Only a handful of countries possess appropriate infrastructure and personnel, whereas the majority have yet to develop such capacity. Resource-constrained environments strongly determines the possibilities of performing research locally, and unidirectional export of biological samples and genetic data remains a concern. Local-regional partnerships, in collaboration with global PD consortia, should form an ethically appropriate solution, which will lead to a reduction in inequality and promote capacity building on the African continent.

Ayodele, KP, Akinboboye EA, Komolafe MA.  2020.  The performance of a low-cost bio-amplifier on 3D human arm movement reconstruction, 2020. Biomedizinische Technik. 65(5) Abstract

Objectives: In this study, the performance of OpenBCI, a low-cost bio-amplifier, is assessed when used for 3D motion reconstruction. Methods: Eleven scalp electrode locations from three subjects were used, with sampling rate of 125 Hz, subsequently band-pass filtered from 0.5 to 40 Hz. After segmentation into epochs, information-rich frequency ranges were determined using filter bank common spatial filter. Simultaneously, the actual hand motions of subjects were captured using a Microsoft Kinect sensor. Multimodal data streams were synchronized using the lab streaming layer (LSL) application. A modified version of an existing multiple linear regression models was employed to learn the relationship between the electroencephalography (EEG) feature input and the recorded kinematic data. To assess system performance with limited data, 10-fold cross validation was used. Results: The most information-rich frequency bands for subjects were found to be in the ranges of 5 - 9 Hz and 33 - 37 Hz. Hand lateralization accuracy for the three subjects were 97.4, 78.7 and 96.9% respectively. 3D position reconstructed with an average correlation coefficient of 0.21, 0.47 and 0.38 respectively along three pre-defined axes, with the corresponding average correlation coefficients for velocity being 0.21, 0.36 and 0.25 respectively. The results compare favourably with a cross-section of existing results, while cost-per-electrode costs were 76% lower than the average per-electrode cost for similar systems and 44% lower than the cheapest previously-reported system. Conclusions: This study has shown that low-cost bio-amplifiers such as the OpenBCI can be used for 3D motion reconstruction tasks.

Aderibigbe, AS, Famurewa OC, Komolafe MA, Omisore AD, Adetiloye VA.  2020.  Sonographic soft tissue arthritic changes associated with post-stroke hemiplegic knee pain: Utility of musculoskeletal ultrasound in a resource-limited setting, 2020. Polish Journal of Radiology. 85(1) Abstract

Purpose: Post-stroke arthritic changes that may compromise rehabilitation have been described in the upper and lower limbs. We aimed at evaluating the soft tissue arthritic changes associated with pain in hemiplegic knees of stroke patients in our environment. Material and methods: Hemiplegic and non-hemiplegic knees of 48 stroke patients as well as both knees of 26 appar-ently healthy controls were evaluated with a 7.5-12 MHz linear ultrasound probe. History of knee pain, and socio-demographic, laboratory, and clinical data were recorded for all study participants. Muscle tone and power as well as functional ambulatory category (FAC) were graded for the stroke patients. Data was analysed using SPSS version 20. Results: Pain was reported more often in hemiplegic than non-hemiplegic knees (n = 16 vs. n = 6, p = 0.021). The fre-quencies of soft tissue arthritic changes found, which included reduced lateral and medial femoral cartilage thickness, suprapatellar effusion, and irregular cartilage-bone margin, were similar between hemiplegic and non-hemiplegic knees (p > 0.05). Suprapatellar effusion and reduced lateral femoral cartilage thickness were more prevalent in the hemiplegic knees compared to the healthy control knees (p < 0.05). Stroke patients with pes anserinus tendinosis had greater risk of hemiplegic knee pain (HKP) when compared to stroke patients without this lesion (OR = 10; 95% CI: 1.7-61). FAC, muscle tone, and power showed no association with HKP. Conclusions: Soft tissue arthritic changes associated with knee pain are comparable between hemiplegic and non-hemi-plegic knees of stroke patients. The risk of knee pain in stroke is higher in the presence of pes anserinus tendinosis.

Ayodele, KP, Ikezogwo WO, Komolafe MA, Ogunbona P.  2020.  Supervised domain generalization for integration of disparate scalp EEG datasets for automatic epileptic seizure detection, 2020. Computers in Biology and Medicine. 120 Abstract

Numerous automatic epileptic seizure detectors (ESDs) with excellent performances have been reported, but they generally experience performance degradation when tested with real-life clinical data. This has been blamed on the scarcity of high-quality training data, which leads to models that generalize poorly. There is consequently interest in methods to improve the quality and quantity of training data for ESDs. This study used a domain generalization approach to combine data from two different datasets for training an ESD, which was thereafter tested on a third dataset. A subspace of the CHB-MIT and TUSZ scalp EEG seizure datasets was extracted using transfer component analysis, based on a reproducing kernel Hilbert space approach. We then used the Azimuthal Equidistant Projection to transform 3D electrode coordinates into 2D space, followed by interpolation using the Clough–Tocher technique to generate 16x16 rasters. We thereafter generated feature vectors, each of which was a sequence of 17 ten-layer 16x16 raster arrays. The vectors were used to train a recurrent-convolutional neural network. The network had a 128-unit long short-term memory layer with inputs from 17 parallel networks each with three stacks of convolutional layers. Testing was based on a private 26-subject dataset, combined with randomly selected subsets of the CHB-MIT and TUSZ datasets. A combined sensitivity of 74.5% was achieved, along with a false positive per hour rate of 0.84, and a latency of 2.32 s. Detection sensitivity on the private dataset was 72.5%. These results compare favorably with results of large-scale validation studies in literature and confirm the viability of this approach to increasing the size of training datasets for ESDs.

Oluwole, OG, Kuivaniemi H, Abrahams S, Haylett WL, Vorster AA, Van Heerden CJ, Kenyon CP, Tabb DL, Fawale MB, Sunmonu TA, Ajose A, Olaogun MO, Rossouw AC, Van Hillegondsberg LS, Carr J, Ross OA, Komolafe MA, Tromp G, Bardien S.  2020.  Targeted next-generation sequencing identifies novel variants in candidate genes for Parkinson's disease in Black South African and Nigerian patients, 2020. BMC Medical Genetics. 21(1) Abstract

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.

Sarfo, FS, Ovbiagele B, Gebregziabher M, Akpa O, Akpalu A, Wahab K, Ogbole G, Akinyemi R, Obiako R, Komolafe M, Owolabi L, Lackland D, Arnett D, Tiwari H, Markus HS, Akinyemi J, Oguntade A, Fawale B, Adeoye A, Olugbo O, Ogunjimi L, Osaigbovo G, Jenkins C, Chukwuonye I, Ajose O, Oyinloye L, Mutiso F, Laryea R, Calys-Tagoe B, Salaam A, Amusa G, Olowookere S, Imoh C, Mande A, Arulogun O, Adekunle F, Appiah L, Balogun O, Singh A, Adeleye O, Ogah O, Makanjuola A, Owusu D, Kolo P, Adebayo O, Agunloye A, Shidali V, Faniyan M, Lakoh S, Diala S, Iheonye H, Efidi C, Sanya E, Sunmonu T, Akintunde A, Owolabi M.  2020.  Unraveling the risk factors for spontaneous intracerebral hemorrhage among West Africans, 2020. Neurology. 94(10) Abstract

ObjectiveTo characterize risk factors for spontaneous intracerebral hemorrhage (sICH) occurrence and severity among West Africans.MethodsThe Stroke Investigative Research and Educational Network (SIREN) study is a multicenter case-control study involving 15 sites in Ghana and Nigeria. Patients were adults ≥18 years old with CT-confirmed sICH with age-, sex-, and ethnicity-matched stroke-free community controls. Standard instruments were used to assess vascular, lifestyle, and psychosocial factors. Factors associated with sICH and its severity were assessed using conditional logistic regression to estimate odds ratios (ORs) and population-attributable risks (PARs) with 95% confidence intervals (CIs) for factors.ResultsOf 2,944 adjudicated stroke cases, 854 were intracerebral hemorrhage (ICH). Mean age of patients with ICH was 54.7 ± 13.9 years, with a male preponderance (63.1%), and 77.3% were nonlobar. Etiologic subtypes of sICH included hypertension (80.9%), structural vascular anomalies (4.0%), cerebral amyloid angiopathy (0.7%), systemic illnesses (0.5%), medication-related (0.4%), and undetermined (13.7%). Eight factors independently associated with sICH occurrence by decreasing order of PAR with their adjusted OR (95% CI) were hypertension, 66.63 (20.78-213.72); dyslipidemia, 2.95 (1.84-4.74); meat consumption, 1.55 (1.01-2.38); family history of CVD, 2.22 (1.41-3.50); nonconsumption of green vegetables, 3.61 (2.07-6.31); diabetes mellitus, 2.11 (1.29-3.46); stress, 1.68 (1.03-2.77); and current tobacco use, 14.27 (2.09-97.47). Factors associated with severe sICH using an NIH Stroke Scale score >15 with adjusted OR (95% CI) were nonconsumption of leafy green vegetables, 2.03 (1.43-2.88); systolic blood pressure for each mm Hg rise, 1.01 (1.00-1.01); presence of midline shift, 1.54 (1.11-2.13); lobar ICH, 1.72 (1.16-2.55); and supratentorial bleeds, 2.17 (1.06-4.46).ConclusionsPopulation-level control of the dominant factors will substantially mitigate the burden of sICH in West Africa.

2019
Salpietro, V, Dixon CL, Guo H, Bello OD, Vandrovcova J, Efthymiou S, Maroofian R, Heimer G, Burglen L, Valence S et al..  2019.  AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders, 2019. Nature Communications. 10(1) Abstract

AMPA receptors (AMPARs) are tetrameric ligand-gated channels made up of combinations of GluA1-4 subunits encoded by GRIA1-4 genes. GluA2 has an especially important role because, following post-transcriptional editing at the Q607 site, it renders heteromultimeric AMPARs Ca2+-impermeable, with a linear relationship between current and trans-membrane voltage. Here, we report heterozygous de novo GRIA2 mutations in 28 unrelated patients with intellectual disability (ID) and neurodevelopmental abnormalities including autism spectrum disorder (ASD), Rett syndrome-like features, and seizures or developmental epileptic encephalopathy (DEE). In functional expression studies, mutations lead to a decrease in agonist-evoked current mediated by mutant subunits compared to wild-type channels. When GluA2 subunits are co-expressed with GluA1, most GRIA2 mutations cause a decreased current amplitude and some also affect voltage rectification. Our results show that de-novo variants in GRIA2 can cause neurodevelopmental disorders, complementing evidence that other genetic causes of ID, ASD and DEE also disrupt glutamatergic synaptic transmission.

Akpalu, A, Gebregziabher M, Ovbiagele B, Sarfo F, Iheonye H, Akinyemi R, Akpa O, Tiwari HK, Arnett D, Wahab K, Lackland D, Abiodun A, Ogbole G, Jenkins C, Arulogun O, Akpalu J, Obiako R, Olowoyo P, Fawale M, Komolafe M, Osaigbovo G, Obiabo Y, Chukwuonye I, Owolabi L, Adebayo P, Sunmonu T, Owolabi M.  2019.  Differential Impact of Risk Factors on Stroke Occurrence Among Men Versus Women in West Africa: The SIREN Study, 2019. Stroke. 50(4) Abstract

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.

Adeoye, AM, Ovbiagele B, Akinyemi JO, Ogah OS, Akinyemi R, Gebregziabher M, Wahab K, Fakunle AG, Akintunde A, Adebayo O, Aje A, Tiwari HK, Arnett D, Agyekum F, Appiah LT, Amusa G, Olunuga TO, Onoja A, Sarfo FS, Akpalu A, Jenkins C, Lackland D, Owolabi L, Komolafe M, Faniyan MM, Arulogun O, Obiako R, Owolabi M.  2019.  Echocardiographic Abnormalities and Determinants of 1-Month Outcome of Stroke Among West Africans in the SIREN Study, 2019. Journal of the American Heart Association. 8(11) Abstract

Background: Little is known about the relationship between echocardiographic abnormalities and outcome among patients with acute stroke. We investigated the pattern and association of baseline echocardiographic variables with 1-month disability and mortality among patients with stroke in the SIREN (Stroke Investigative Research and Education Network) study. Methods and Results: We enrolled and followed up consecutive 1020 adult patients with acute stroke with baseline transthoracic echocardiography from west Africa. To explore the relationship between echocardiographic variables and 1-month disability (using modified Rankin scale >3) and fatality, regression models were fitted. Relative risks were computed with 95% CIs. The participants comprised 60% men with a mean age of 59.2±14.6 years. Ischemic stroke was associated with smaller aortic root diameter (30.2 versus 32.5, P=0.018) and septal (16.8 versus 19.1, P<0.001) and posterior wall thickness at systole (18.9 versus 21.5, P=0.004). Over 90% of patients with stroke had abnormal left ventricular (LV) geometry with eccentric hypertrophy predominating (56.1%). Of 13 candidate variables investigated, only baseline abnormal LV geometry (concentric hypertrophy) was weakly associated with 1-month disability (unadjusted relative risk, 1.80; 95% CI, 0.97–5.73). Severe LV systolic dysfunction was significantly associated with increased 1-month mortality (unadjusted relative risk, 3.05; 95% CI, 1.36–6.83). Conclusions: Nine of 10 patients with acute stroke had abnormal LV geometry and a third had systolic dysfunction. Severe LV systolic dysfunction was significantly associated with 1 month mortality. Larger studies are required to establish the independent effect and unravel predictive accuracy of this association.

Akinyemi, RO, Sarfo FS, Akinyemi J, Singh A, Onoja Akpa M, Akpalu A, Owolabi L, Adeoye AM, Obiako R, Wahab K, Sanya E, Komolafe M, Ogbole G, Fawale M, Adebayo P, Osaigbovo G, Sunmonu T, Olowoyo P, Chukwuonye I, Obiabo Y, Adeniji O, Fakunle G, Melikam E, Saulson R, Yaria J, Uwanruochi K, Ibinaiye P, Amusa GA, Yahaya IS, Dambatta AH, Faniyan M, Olowoniyi P, Bock-Oruma A, Joseph OC, Oguntade A, Kolo P, Laryea R, Lakoh S, Uvere E, Farombi T, Akpalu J, Oyinloye O, Appiah L, Calys-Tagoe B, Shidali V, Tabari NA, Adebayo O, Efidi R, Adeleye O, Owusu D, Ogunjimi L, Aridegbe O, Imoh CL, Sanni T, Gebreziabher M, Hemant T, Arulogun O, Ogunniyi A, Jenkins C, Owolabi M, Ovbiagele B.  2019.  Knowledge, attitudes and practices of West Africans on genetic studies of stroke: Evidence from the SIREN Study, 2019. International Journal of Stroke. 14(1) Abstract

Background: It is crucial to assess genomic literacy related to stroke among Africans in preparation for the ethical, legal and societal implications of the genetic revolution which has begun in Africa. Objective: To assess the knowledge, attitudes and practices (KAP) of West Africans about stroke genetic studies. Methods: A comparative cross-sectional study was conducted among stroke patients and stroke-free controls recruited across 15 sites in Ghana and Nigeria. Participants' knowledge of heritability of stroke, willingness to undergo genetic testing and perception of the potential benefits of stroke genetic research were assessed using interviewer-administered questionnaire. Descriptive, frequency distribution and multiple regression analyses were performed. Results: Only 49% of 2029 stroke patients and 57% of 2603 stroke-free individuals knew that stroke was a heritable disorder. Among those who knew, 90% were willing to undergo genetic testing. Knowledge of stroke heritability was associated with having at least post-secondary education (OR 1.51, 1.25–1.81) and a family history of stroke (OR 1.20, 1.03–1.39) while Islamic religion (OR=0.82, CI: 0.72–0.94), being currently unmarried (OR = 0.81, CI: 0.70–0.92), and alcohol use (OR = 0.78, CI: 0.67–0.91) were associated with lower odds of awareness of stroke as a heritable disorder. Willingness to undergo genetic testing for stroke was associated with having a family history of stroke (OR 1.34, 1.03–1.74) but inversely associated with a medical history of high blood pressure (OR = 0.79, 0.65–0.96). Conclusion: To further improve knowledge of stroke heritability and willingness to embrace genetic testing for stroke, individuals with less formal education, history of high blood pressure and no family history of stroke require targeted interventions.

Oluwole, OG, Kuivaniemi H, Carr JA, Ross OA, Olaogun MOB, Bardien S, Komolafe MA.  2019.  Parkinson's disease in Nigeria: A review of published studies and recommendations for future research, 2019. Parkinsonism and Related Disorders. 62 Abstract

Parkinson's disease (PD) affects 1–2% of individuals above 60 years amounting to over 7 million people worldwide. Thus, PD has become an important contributor to the neurological disease burden. Nigeria is the most populous country in Africa, and alarmingly, approximately 5.25 million Nigerians are above 65 years and are therefore at risk for developing PD. We carried out a critical review of published literature on PD in Nigeria to summarize the findings and to evaluate gaps in knowledge. Seven electronic databases were searched for studies published in English before 18th July 2018. Search terms were [”Parkinson's disease” OR “Parkinson disease” OR “parkinsonian disorders” OR “Parkinsonism”] AND “Nigeria”. A total of 44 articles (including eight reviews) published since 1969 were identified and reviewed. Amongst the original research articles, most (23) were on PD symptoms or prevalence. There were only two studies on genetics and two on environmental factors. The estimated crude prevalence of PD in Nigeria was lower (10–249/100 000) compared to studies published in Europe (65.6–12 500/100 000). Our findings suggest that PD is under-diagnosed in Nigeria. Possible environmental risk factors identified include blacksmithing and well-water contaminated with trace metals. Given the rising numbers of the ageing population in Nigeria, more studies to evaluate the prevalence and causes of PD in this country are urgently needed. To this end, more funding, resources and a workforce of well-trained neurologists and scientists are essential to manage the impending health burden of PD and related disorders in this country.

Chelban, V, Wilson MP, Warman Chardon J, Vandrovcova J, Zanetti MN, Zamba-Papanicolaou E, Efthymiou S, Pope S, Conte MR, Abis G et al..  2019.  PDXK mutations cause polyneuropathy responsive to pyridoxal 5'-phosphate supplementation, 2019. Annals of Neurology. 86(2) Abstract

Objective: To identify disease-causing variants in autosomal recessive axonal polyneuropathy with optic atrophy and provide targeted replacement therapy. Methods: We performed genome-wide sequencing, homozygosity mapping, and segregation analysis for novel disease-causing gene discovery. We used circular dichroism to show secondary structure changes and isothermal titration calorimetry to investigate the impact of variants on adenosine triphosphate (ATP) binding. Pathogenicity was further supported by enzymatic assays and mass spectroscopy on recombinant protein, patient-derived fibroblasts, plasma, and erythrocytes. Response to supplementation was measured with clinical validated rating scales, electrophysiology, and biochemical quantification. Results: We identified biallelic mutations in PDXK in 5 individuals from 2 unrelated families with primary axonal polyneuropathy and optic atrophy. The natural history of this disorder suggests that untreated, affected individuals become wheelchair-bound and blind. We identified conformational rearrangement in the mutant enzyme around the ATP-binding pocket. Low PDXK ATP binding resulted in decreased erythrocyte PDXK activity and low pyridoxal 5′-phosphate (PLP) concentrations. We rescued the clinical and biochemical profile with PLP supplementation in 1 family, improvement in power, pain, and fatigue contributing to patients regaining their ability to walk independently during the first year of PLP normalization. Interpretation: We show that mutations in PDXK cause autosomal recessive axonal peripheral polyneuropathy leading to disease via reduced PDXK enzymatic activity and low PLP. We show that the biochemical profile can be rescued with PLP supplementation associated with clinical improvement. As B6 is a cofactor in diverse essential biological pathways, our findings may have direct implications for neuropathies of unknown etiology characterized by reduced PLP levels. ANN NEUROL 2019;86:225–240.

2018
Akinyemi, R, Tiwari HK, Arnett DK, Ovbiagele B, Irvin MR, Wahab K, Sarfo F, Srinivasasainagendra V, Adeoye A, Perry RT, Akpalu A, Jenkins C, Arulogun O, Gebregziabher M, Owolabi L, Obiako R, Sanya E, Komolafe M, Fawale M, Adebayo P, Osaigbovo G, Sunmonu T, Olowoyo P, Chukwuonye I, Obiabo Y, Onoja A, Akinyemi J, Ogbole G, Melikam S, Saulson R, Owolabi M.  2018.  APOL1, CDKN2A/CDKN2B, and HDAC9 polymorphisms and small vessel ischemic stroke, 2018. Acta Neurologica Scandinavica. 137(1) Abstract

Objective: Worldwide, the highest frequencies of APOL1-associated kidney variants are found in indigenous West Africans among whom small vessel disease (SVD) ischemic stroke is the most common stroke phenotype. The objective of this study was to investigate the association and effect sizes of 23 selected SNPs in 14 genes of relevance, including the APOL1 G1 variants, with the occurrence of SVD ischemic stroke among indigenous West African participants in the Stroke Investigative Research and Education Network (SIREN) Study. Materials and Methods: Cases were consecutively recruited consenting adults (aged 18 years or older) with neuroimaging—confirmed first clinical stroke. Stroke-free controls were ascertained using a locally validated version of the Questionnaire for Verifying Stroke-Free Status (QVSFS). Logistic regression models adjusting for known vascular risk factors were fitted to assess the associations of the 23 SNPs in rigorously phenotyped cases (N = 154) of SVD ischemic stroke and stroke-free (N = 483) controls. Results: Apolipoprotein L1 (APOL1) rs73885319 (OR = 1.52; CI: 1.09-2.13, P-value =.013), rs2383207 in CDKN2A/CDKN2B (OR = 3.08; CI: 1.15-8.26, P –value =.026) and rs2107595 (OR = 1.70; CI: 1.12-2.60, P-value =.014) and rs28688791 (OR = 1.52; CI: 1.03-2.26, P-value =.036) in HDAC9 gene were associated with SVD stroke at 0.05 significance level. Polymorphisms in other genes did not show significant associations. Conclusion: This is the first report of a specific association of APOL1 with a stroke subtype. Further research is needed to confirm these initial findings and deepen understanding of the genetics of stroke in people of African ancestry with possible implications for other ancestries as all humans originated from Africa.

Omisore, AD, Famurewa OC, Komolafe MA, Asaleye CM, Fawale MB, Afolabi BI.  2018.  Association of traditional cardiovascular risk factors with carotid atherosclerosis among adults at a teaching hospital in south-western Nigeria, 2018. Cardiovascular Journal of Africa. 29(3) Abstract

Background: Traditional cardiovascular risk factors (CVRFs), which include age, gender, hypertension, diabetes mellitus, dyslipidaemia, smoking, alcohol consumption, chronic kidney disease and obesity, have been shown to be associated with atherosclerosis. We aimed to evaluate the impact of traditional CVRFs on carotid atherosclerosis (CA) in a sample of Nigerian adults. Methods: We examined 162 subjects with traditional CVRFs in a cross-sectional study. Demographic and clinical data, including history of hypertension, diabetes mellitus, smoking, alcohol intake and chronic kidney disease, as well as systolic and diastolic blood pressure, weight and height were collected. Serum creatinine, fasting blood glucose and lipid profiles were also determined. Carotid intima-media thickness (CIMT) and presence of carotid plaque (CP) were evaluated by high-frequency B-mode ultrasound. Chi-squared and regression analyses were carried out to determine associations between variables of C1MT and CVRF. Results: Increased CIMT was associated with all CVRFs (p < 0.05) except gender (p > 0.05), while CP was associated with older age, obesity, hypertension and dyslipidaemia (p < 0.05). We found prevalence of increased CIMT was 53.7%, while that of CP was 16.1%. The prevalence of CA (increased CIMT and CP) also increased with increasing number of CVRFs in the subjects. Age > 50 years, hypertension, dyslipidaemia, obesity and alcohol intake explained 78.7% of variance in CIMT, while age > 50 years and hypertension explained 38.0% of variance in CP. Conclusions: CA was associated with presence and increasing number of traditional CVRFs. A significant percentage of variance in CA was, however, unexplained by traditional CVRFs.