Godwin Ogbole

Profile and determinants of vascular cognitive impairment in African stroke survivors: The CogFAST Nigeria Study

OBJECTIVE Sub-Saharan Africa faces a potential epidemic of non-communicable diseases including stroke and dementia but little is known about the burden of stroke-related cognitive dysfunction. We assessed the baseline profile and factors associated with vascular cognitive impairment (VCI) in stroke survivors participating in the Cognitive Function After STroke (CogFAST) Nigeria Study. METHODS We recruited 217 subjects (>45 years old) comprising 143 stroke survivors and 74 demographically matched stroke-free healthy controls. We obtained demographic, clinical and lifestyle information and assessed the cognitive status of the subjects at baseline three months after stroke. Standard neuropsychological tests included the Vascular Neuropsychological Battery, which assessed executive function/mental speed, memory, language, and visuospatial/visuoconstructive functioning. Cognitive impairment and dementia were defined based on the AHA/ASA VCI guidelines and the DSM IV criteria. RESULTS Among the stroke survivors (mean ag e= 60.4+9.5 years, 43.4% female, mean number of years of education = 9.4+5.6 years, median modified Rankin score = 2), 57 (39.9%) had cognitive impairment no dementia while 12 (8.4%) were demented at baseline. Multivariate analysis revealed that older age [OR = 1.05 (1.00-1.09)], low education [OR = 5.09 (2.17-11.95)], pre-stroke cognitive decline [OR = 4.51 (1.20-16.88)] and medial temporal lobe atrophy [OR = 2.25 (1.16-4.35)] were independently associated with cognitive dysfunction whereas pre-stroke daily intake of fish [p = 0.022, OR = 0.39 (0.15-0.89)] was inversely associated. CONCLUSIONS These results suggest a high frequency of early VCI in older Nigerian stroke survivors. Apart from aging, associated neurodegeneration and cognitive decline, educational level and pre-stroke diet particularly fish consumption were identified as modifiable factors. This emphasizes the vital role of education and healthy nutrition in building reserves to ameliorate cognitive dysfunction after stroke.

Phenotyping Stroke in Sub-Saharan Africa: Stroke Investigative Research and Education Network (SIREN) Phenomics Protocol

Background: As the second leading cause of death and the leading cause of adult-onset disability, stroke is a major public health concern particularly pertinent in Sub-Saharan Africa (SSA), where nearly 80% of all global stroke mortalities occur, and stroke burden is projected to increase in the coming decades. However, traditional and emerging risk factors for stroke in SSA have not been well characterized, thus limiting efforts at curbing its devastating toll. The Stroke Investigative Research and Education Network (SIREN) project is aimed at comprehensively evaluating the key environmental and genomic risk factors for stroke (and its subtypes) in SSA while simultaneously building capacities in phenomics, biobanking, genomics, biostatistics, and bioinformatics for brain research. Methods: SIREN is a transnational, multicentre, hospital and community-based study involving 3,000 cases and 3,000 controls recruited from 8 sites in Ghana and Nigeria. Cases will be hospital-based patients with first stroke within 10 days of onset in whom neurovascular imaging will be performed. Etiological and topographical stroke subtypes will be documented for all cases. Controls will be hospital- and community-based participants, matched to cases on the basis of gender, ethnicity, and age (±5 years). Information will be collected on known and proposed emerging risk factors for stroke. Study Significance: SIREN is the largest study of stroke in Africa to date. It is anticipated that it will shed light on the phenotypic characteristics and risk factors of stroke and ultimately provide evidence base for strategic interventions to curtail the burgeoning burden of stroke on the sub-continent.

Multilingual Validation of the Questionnaire for Verifying Stroke-Free Status in West Africa

Background and Purpose— The Questionnaire for Verifying Stroke-Free Status (QVSFS), a method for verifying stroke-free status in participants of clinical, epidemiological, and genetic studies, has not been validated in low-income settings where populations have limited knowledge of stroke symptoms. We aimed to validate QVSFS in 3 languages, Yoruba, Hausa and Akan, for ascertainment of stroke-free status of control subjects enrolled in an on-going stroke epidemiological study in West Africa. Methods— Data were collected using a cross-sectional study design where 384 participants were consecutively recruited from neurology and general medicine clinics of 5 tertiary referral hospitals in Nigeria and Ghana. Ascertainment of stroke status was by neurologists using structured neurological examination, review of case records, and neuroimaging (gold standard). Relative performance of QVSFS without and with pictures of stroke symptoms (pictograms) was assessed using sensitivity, specificity, positive predictive value, and negative predictive value. Results— The overall median age of the study participants was 54 years and 48.4% were males. Of 165 stroke cases identified by gold standard, 98% were determined to have had stroke, whereas of 219 without stroke 87% were determined to be stroke-free by QVSFS. Negative predictive value of the QVSFS across the 3 languages was 0.97 (range, 0.93–1.00), sensitivity, specificity, and positive predictive value were 0.98, 0.82, and 0.80, respectively. Agreement between the questionnaire with and without the pictogram was excellent/strong with Cohen k=0.92. Conclusions— QVSFS is a valid tool for verifying stroke-free status across culturally diverse populations in West Africa.

Dominant modifiable risk factors for stroke in Ghana and Nigeria (SIREN): a case-control study

Summary Background Sub-Saharan Africa has the highest incidence, prevalence, and fatality from stroke globally. Yet, only little information about context-specific risk factors for prioritising interventions to reduce the stroke burden in sub-Saharan Africa is available. We aimed to identify and characterise the effect of the top modifiable risk factors for stroke in sub-Saharan Africa. Methods The Stroke Investigative Research and Educational Network (SIREN) study is a multicentre, case-control study done at 15 sites in Nigeria and Ghana. Cases were adults (aged ≥18 years) with stroke confirmed by CT or MRI. Controls were age-matched and gender-matched stroke-free adults (aged ≥18 years) recruited from the communities in catchment areas of cases. Comprehensive assessment for vascular, lifestyle, and psychosocial factors was done using standard instruments. We used conditional logistic regression to estimate odds ratios (ORs) and population-attributable risks (PARs) with 95% CIs. Findings Between Aug 28, 2014, and June 15, 2017, we enrolled 2118 case-control pairs (1192 [56%] men) with mean ages of 59.0 years (SD 13.8) for cases and 57.8 years (13.7) for controls. 1430 (68%) had ischaemic stoke, 682 (32%) had haemorrhagic stroke, and six (<1%) had discrete ischaemic and haemorrhagic lesions. 98.2% (95% CI 97.2–99.0) of adjusted PAR of stroke was associated with 11 potentially modifiable risk factors with ORs and PARs in descending order of PAR of 19.36 (95% CI 12.11–30.93) and 90.8% (95% CI 87.9–93.7) for hypertension, 1.85 (1.44–2.38) and 35.8% (25.3–46.2) for dyslipidaemia, 1.59 (1.19–2.13) and 31.1% (13.3–48.9) for regular meat consumption, 1.48 (1.13–1.94) and 26.5% (12.9–40.2) for elevated waist-to-hip ratio, 2.58 (1.98–3.37) and 22.1% (17.8–26.4) for diabetes, 2.43 (1.81–3.26) and 18.2% (14.1–22.3) for low green leafy vegetable consumption, 1.89 (1.40–2.54) and 11.6% (6.6–16.7) for stress, 2.14 (1.34–3.43) and 5.3% (3.3–7.3) for added salt at the table, 1.65 (1.09–2.49) and 4.3% (0.6–7.9) for cardiac disease, 2.13 (1.12–4.05) and 2.4% (0.7–4.1) for physical inactivity, and 4.42 (1.75–11.16) and 2.3% (1.5–3.1) for current cigarette smoking. Ten of these factors were associated with ischaemic stroke and six with haemorrhagic stroke occurrence. Interpretation Implementation of interventions targeting these leading risk factors at the population level should substantially curtail the burden of stroke among Africans. Funding National Institutes of Health.

Stroke in Indigenous Africans, African Americans, and European Americans

Background and Purpose— The relative contributions of racial and geographic factors to higher risk of stroke in people of African ancestry have not been unraveled. We compared stroke type and contributions of vascular risk factors among indigenous Africans (IA), African Americans (AA), and European Americans (EA). Methods— SIREN (Stroke Investigative Research and Educational Network) is a large multinational case–control study in West Africa—the ancestral home of 71% AA—whereas REGARDS (Reasons for Geographic and Racial Differences in Stroke) is a cohort study including AA and EA in the United States. Using harmonized assessments and standard definitions, we compared data on stroke type and established risk factors for stroke in acute stroke cases aged ≥55 years in both studies. Results— There were 811 IA, 452 AA, and 665 EA stroke subjects, with mean age of 68.0±9.3, 73.0±8.3, and 76.0±8.3 years, respectively (P<0.0001). Hemorrhagic stroke was more frequent among IA (27%) compared with AA (8%) and EA (5.4%; P<0.001). Lacunar strokes were more prevalent in IA (47.1%), followed by AA (35.1%) and then EA (21.0%; P<0.0001). The frequency of hypertension in decreasing order was IA (92.8%), followed by AA (82.5%) and then EA (64.2%; P<0.0001) and similarly for diabetes mellitus IA (38.3%), AA (36.8%), and EA (21.0%; P<0.0001). Premorbid sedentary lifestyle was similar in AA (37.7%) and EA (34.0%) but lower frequency in IA (8.0%). Conclusions— Environmental risk factors such as sedentary lifestyle may contribute to the higher proportion of ischemic stroke in AA compared with IA, whereas racial factors may contribute to the higher proportion of hypertension and diabetes mellitus among stroke subjects of African ancestry.

Low field MR imaging of sellar and parasellar lesions: experience in a developing country hospital.

BACKGROUND Magnetic resonance imaging (MRI), an advancement which followed computed tomography (CT) is expensive and inaccessible in most developing countries. However it is the procedure of choice in evaluating sellar and parasellar lesions. Its major advantages are its superior soft tissue contrast differentiation, its capacity for multiplanar imaging and nonexistence of ionising radiation. Its use is relatively new in Nigeria, a developing economy in Africa. Since its introduction in 2005, it has been utilised extensively for neuroimaging at the University College Hospital (UCH), Ibadan; a large hospital in south-western Nigeria. OBJECTIVE To review the role and pattern of low field MR Imaging in sellar and parasellar lesions presenting to a tertiary care centre in Nigeria. METHODS All 62 patients with clinically suspected sellar and parasellar masses, referred to the Department of Radiology, UCH Ibadan for MRI between December 2006 and January 2010 were retrospectively analysed. The examinations were performed using an open 0.2T permanent magnet MR unit. T1W, T2W, T2/FLAIR, TOF and T1W post gadolinium DTPA sequences of the sellar region were obtained. RESULTS Of the 62 patients, there were 27 males and 35 females. The modal age group was 40-49 years with a mean age of 39.94 years (±16.65 years). Twenty-four cases (38.7%) had histological diagnosis, of which 20 (83.3%) were consistent with initial MRI diagnosis. Pituitary adenomas were the commonest (58.06%) lesions of the sellar and parasellar regions. Others include parasellar meningiomas, cranipharyngiomas, and giant aneurysms. Headache and visual impairment were the major presenting features and showed no significant correlation with tumour size. CONCLUSION The use of low field MRI in the diagnostic evaluation of patients with suspected sellar or parasellar lesions in developing countries of low economic resource is commendable as it provides beneficial outcomes in management.

White matter changes on magnetic resonance imaging: a risk factor for stroke in an African population?

BACKGROUND White matter changes are frequently observed incidental findings in elderly individuals. Many studies in Europe and the United States have assessed the association of white matter changes with stroke and other diseases. No similar study has been conducted in sub-Saharan Africa, where risk factors for stroke differ. Our objective was to explore the association between severity of white matter changes (based on visual rating scales) and stroke in a Nigerian population. METHODS Magnetic resonance imaging (MRI) scans of 50 patients were retrospectively assessed and scored using 3 different visual rating scales (by Fazekas et al, Scheltens et al, and Manolio et al). The scores were classified as either mild or severe. Clinical indications and MRI scan results were classified into vascular (stroke) and nonvascular groups. The association between severity of white matter changes and stroke on MRI was explored using the Student t test, the Chi-square test, and multiple regression analysis at an alpha level of .05. RESULTS White matter changes were consistently and significantly more severe in patients with stroke than in patients without stroke (.01 ≤ P < .001; odds ratios 4.58 and 13.3, respectively) using the 3 visual rating scales. This finding was independent of age and gender as confirmed by regression analysis (adjusted odds ratios 4.8 and 9.2; .015 ≤ P ≤ .003). CONCLUSIONS Our findings suggest that severity of white matter changes in Nigerians may be a significant risk factor for stroke independent of age and gender. Prospective larger studies will be required to confirm its role in predicting stroke and stroke recurrence independent of other vascular risk factors, such as hypertension, diabetes, and cardiac diseases.

APOL1, CDKN2A/CDKN2B, and HDAC9 polymorphisms and small vessel ischemic stroke

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.

Magnetic resonance imaging: Clinical experience with an open low-field-strength scanner in a resource challenged African state

Introduction: Despite the fact that an magnetic resonance imaging (MRI) has been in clinical use for over 20 years, its use and availability in Nigeria, a West African state, is still extremely low. Hence, only few publications are available on the clinical experience with MRI from Nigeria. We set out to evaluate our initial clinical experience with a low-field-strength MRI in a Nigerias foremost university hospital. Materials and Methods: A retrospective review of all studies, performed with an open 0.2 Tesla MAGNETOM Concerto (Siemens Medical) MRI scanner over a 5-year period (2006 - 2010) was conducted. All patients with complete records were evaluated for their clinical and demographic characteristics. Results: The records of 799 MRI studies were available. Patients’ ages ranged from 1 day to 90 years, with a mean of 40.1 years (± 20.7 SD). There were 463 (57.9%) males and 336 (42.1%) females. Over 90% of the studies were requested to evaluate brain or spine lesions. Low back pain represented the commonest (161/799, 20.7%) clinical indication for MRI. The largest number of patients was referred by physicians from surgical specialties (65.6%). Conclusion: The awareness and competence for proper use of MRI in Nigeria appears high. Low back pain is the commonest indication for MRI in our institution, and surgeons make a greater use of the facility. The provision of high-signal strength MRI may be beneficial in making a wider range of applications available to clinicians.

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 Cohens 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.