Potential diagnostic challenges of intracerebral hemorrhage as an index presentation of metastatic choriocarcinoma: A case series.

Key Clinical Message: In young women presenting with atypical features of intracerebral hemorrhage, metastatic choriocarcinoma should be considered as a differential diagnosis. In resource-poor settings, a high index of suspicion and serum ß-hCG are crucial for diagnosis. Abstract: Intracerebral hemorrhage in the young is rarely caused by metastatic choriocarcinoma. Diagnosis of this condition may be particularly challenging in resource-poor settings where access to diagnostic technologies may be limited. We present a case series of three young females diagnosed with metastatic choriocarcinoma after initially presenting with intracerebral hemorrhage, each demonstrating unique clinical manifestations. We aim to highlight the diagnostic considerations in the management of this infrequently encountered cause of intracerebral hemorrhage, especially in resource-constrained settings. Case 1 involved a 21-year-old woman who was initially diagnosed with intracerebral hemorrhage likely of tumoral origin from an unknown primary source. Further evaluation revealed extremely high levels of ß-hCG and features suggestive of an intrauterine malignancy, which led to a diagnosis of metastatic choriocarcinoma. This further became complicated by pulmonary embolism. Unfortunately, she succumbed to respiratory failure during treatment. Case 2 is a young woman who presented to the emergency unit and was managed as a case of lobar intracerebral hemorrhage. Further checks revealed a previous history of hysterectomy done on account of placental site trophoblastic tumor, which promoted an evaluation for choriocarcinoma. Case 3 involved a 20-year-old patient who initially presented with headache and vomiting. An enhanced magnetic resonance imaging showed a large subacute right temporal occipital subependymal hemorrhage with mass effect. After probing further, we discovered that she underwent exploratory laparotomy for suspected ruptured ectopic gestation, which later turned out to be a gestational trophoblastic neoplasia. After further evaluation a diagnosis of choriocarcinoma with brain metastasis. Our case series emphasizes the importance of having a high index suspicion in young females who present with atypical features of ICH. The varied clinical scenarios highlight the challenges in diagnosing young females. It also underscores the critical role of serum ß-hCG, especially in resource-limited settings where biopsies are not readily available. Building a repository of these diverse manifestations is essential for increasing the index of suspicion and ultimately improving patient outcomes.

Stroke occurrence by hypertension treatment status in Ghana and Nigeria: A case-control study.

BACKGROUND: Hypertension is preeminent among the vascular risk factors for stroke occurrence. The wide gaps in awareness, detection, treatment, and control rates of hypertension are fueling an epidemic of stroke in sub-Saharan Africa. PURPOSE: To quantify the contribution of untreated, treated but uncontrolled, and controlled hypertension to stroke occurrence in Ghana and Nigeria. METHODS: The Stroke Investigative Research and Educational Network (SIREN) is a case-control study across 16 study sites in Ghana and Nigeria. Cases were acute stroke (n = 3684) with age- and sex-matched stroke-free controls (n = 3684). We evaluated the associations of untreated hypertension, treated but uncontrolled hypertension, and controlled hypertension at BP of <140/90 mmHg with risk of stroke occurrence. We assessed the adjusted odds ratio and population-attributable risk of hypertension treatment control status associated with stroke occurrence. RESULTS: The frequencies of no hypertension, untreated hypertension, treated but uncontrolled hypertension and controlled hypertension among stroke cases were 4.0%, 47.7%, 37.1%, and 9.2% vs 40.7%, 34.9%, 15.9%, and 7.7% respectively among stroke-free controls, p < 0.0001. The aOR and PAR (95% CI) for untreated hypertension were 6.58 (5.15-8.41) and 35.4% (33.4-37.4); treated but uncontrolled hypertension was 9.95 (7.60-13.02) and 35.9% (34.2-37.5); and controlled hypertension 5.37 (3.90-7.41) and 8.5% (7.6-9.5) respectively. Untreated hypertension contributed a PAR of 47.5% to the occurrence of intracerebral hemorrhage vs 29.5% for ischemic stroke. The aOR of untreated hypertension for stroke occurrence was 13.31 (7.64-23.19) for <50 years; 7.14 (4.51-11.31) for 50-64 years; and 3.48 (2.28-5.30) for 65 years or more. CONCLUSION: The contribution of untreated hypertension and treated but uncontrolled hypertension to stroke occurrence among indigenous Africans is substantial. Implementing targeted interventions that address gaps in hypertension prevention and treatment, involving the local population, healthcare providers, and policymakers, can potentially substantially reduce the escalating burden of strokes in Africa.

Epigenetics as a target to mitigate excess stroke risk in people of African ancestry: A scoping review.

BACKGROUND: Globally, individuals of African ancestry have a relatively greater stroke preponderance compared to other racial/ethnic groups. The higher prevalence of traditional stroke risk factors in this population, however, only partially explains this longstanding disparity. Epigenetic signatures are transgenerational and could be a plausible therapeutic target to further bend the stroke disparities curve for people of African ancestry. There is, however, limited data on epigenetics and stroke risk in this population. PURPOSE: To examine existing evidence and knowledge gaps on the potential contribution of epigenetics to excess stroke risk in people of African ancestry and avenues for mitigation. MATERIALS AND METHODS: We conducted a scoping review of studies published between January 2003 and July 2023, on epigenetics and stroke risk. We then summarized our findings, highlighting the results for people of African ancestry. RESULTS: Of 104 studies, there were only 6 studies that specifically looked at epigenetic mechanisms and stroke risk in people of African ancestry. Results of these studies show how patterns of DNA methylation and non-coding RNA interact with lifestyle choices, xenobiotics, and FVIII levels to raise stroke risk in people of African ancestry. However, no studies evaluated epigenetic patterns as actionable targets for the influence of psychosocial stressors or social context and excess stroke risk in this population (versus others). Also, no studies interrogated the role of established or novel therapeutic agents with the potential to reprogram DNA by adding or removing epigenetic markers in people of African ancestry. CONCLUSION: Epigenetics potentially offers a promising target for modifying the effects of lifestyle, environmental exposures, and other factors that differentially affect people of African ancestry and place them at relatively greater stroke risk compared to other populations. Studies that precisely assess the pathways by which epigenetic mechanisms modulate population-specific disparities in the risk of stroke are needed.

Deciphering the contextual barriers to mainstreaming the implementation of stroke thrombolysis in a Ghanaian hospital: Findings from the activate mixed-methods study.

BACKGROUND: Each year, stroke-related death and disability claim over 143 million years of healthy life globally. Despite accounting for much of the global stroke burden, acute stroke care in Low-and-Middle-Income Countries remains suboptimal. Thrombolysis, an effective treatment option for stroke, is only received by a minority of stroke patients in these settings. AIM: To determine the context-specific barriers and facilitators for the implementation of mainstream stroke thrombolysis in a Ghanaian hospital. METHODS: We employed a mixed-methods approach involving key stakeholders (recipients, providers, and leaders) in the acute stroke care continuum. Surveys were administered to acute stroke patients, and in-depth key informant interviews were conducted with experts in stroke care, including a neurologist, medical director, neurology residents, a stroke nurse, emergency physicians, a radiologist, and a pharmacist. The data collected from these interviews were transcribed and analysed using content analysis with the CFIR (Consolidated Framework for Implementation Research) model as a guiding template. Two independent coders were involved in the analysis process to ensure reliability and accuracy. RESULTS: The stroke thrombolysis rate over a 6-month period was 0.83% (2 out of 242), with an average door-to-needle time among thrombolyzed patients being 2 hours, 37 minutes. Only 12.8% of patients (31 out of 242) presented within 4.5 hours of stroke symptom onset. The most significant obstacle to the implementation of acute stroke thrombolysis was related to the characteristics of the individuals involved, notably delays in presenting to the hospital among stroke patients due to a lack of knowledge about stroke symptoms and cultural beliefs. Additionally, a significant bottleneck that contributed to the discrepancy between the number of patients who presented within the 4.5-6 hour window and the number of patients who actually received thrombolysis was the inability to pay for the cost of thrombolytic agents. This was followed by challenges in the implementation processes. CONCLUSIONS: Addressing challenges related to stroke awareness, and financial constraints via multi-level stakeholder engagement, and enactment of stroke protocols are crucial steps in ensuring a successful implementation of a stroke thrombolysis program in a resource-limited setting.

Prevalence and predictors of low folate levels among stroke survivors in a country without mandatory folate food fortification: Analysis of a Ghanaian sample.

BACKGROUND: While additional folic acid (FA) treatment has a neutral effect on lowering overall vascular risk in countries that mandate FA fortification of food, meta-analytic data suggest that folate supplementation reduces stroke risk in certain patient subgroups, and among people living in countries without mandatory folate food fortification. However, the burden of folate deficiency among adults with stroke in the world's poorest continent is unknown. PURPOSE: To assess the prevalence and predictors of folate deficiency among recent ischemic stroke survivors. METHODS: We analyzed data among consecutively encountered ischemic stroke patients aged ≥18 years at a tertiary medical center in Kumasi, Ghana between 10/2020 - 08/2021. We identified a modest sample of stroke free adults to serve as a comparator group. Fasting serum folate was measured using a radioimmunoassay and a cut-off of 4ng/mL used to define folate deficiency. Factors associated with serum folate concentration were assessed using a multilinear regression model. RESULTS: Comparing stroke cases (n = 116) with stroke-free comparators (n = 20), mean folate concentration was lower among stroke cases (7 ng/ml vs. 10.2 ng/ml, p = 0.004). Frequency of folate deficiency was higher among stroke cases vs. stroke-free controls (31% vs 5%, p = 0.02). Male sex (beta coefficient of -2.6 (95% CI: -4.2, -0.9) and LDL (ß: -0.76; -1.4, -0.07) were significantly associated with serum folate concentration. CONCLUSION: Almost one in three ischemic stroke survivors have folate deficiency potentially accentuating their risk for further adverse atherosclerotic events in a setting without folate fortification. A clinical trial of folate supplementation among stroke survivors is warranted.

Participation by patients from low- and middle-income countries (LMICs) in trial evidence supporting secondary stroke prevention guideline recommendations.

BACKGROUND: One out of every four strokes is a highly preventable recurrent stroke. However, while low-and-middle-income countries (LMICs) experience a disproportionate global burden of stroke, individuals in these regions seldomly participate in pivotal clinical trials, which form the basis for international expert consensus guideline recommendations. OBJECTIVE: To evaluate a contemporary and globally prominent expert consensus secondary stroke prevention guideline statement for the participation of clinical trial subjects recruited from LMICs in formulating key therapeutic recommendations. METHODS: We examined the 2021 American Heart Association/American Stroke Association Guideline for the Prevention of Stroke in Patients with Stroke and TIA. All randomized controlled trials (RCTs) cited in the Guideline were independently reviewed by two authors for study populations and participating countries with a focus on trials for vascular risk factor control and management by underlying stroke mechanism. We also reviewed all cited systematic reviews and meta-analyses for the original RCTs. RESULTS: Among 320 secondary stroke prevention clinical trials, 262 (82%) focused on vascular risk control addressing diabetes (n = 26), hypertension (n = 23), obstructive sleep apnea (n = 13), dyslipidaemia (n = 10), lifestyle (n = 188) and obesity (n = 2); and 58 focused on stroke mechanism management including atrial fibrillation (n = 10), large vessel atherosclerosis (n = 45) and small vessel disease (n = 3). Overall, 53 of 320 studies (16.6%) had contributions from LMICs ranging from 55.6% for dyslipidemia, 40.7% for diabetes, 26.1% for hypertension, 15.4% for OSA, 6.4% for lifestyle, 0% for obesity, and by mechanism: 60.0% for atrial fibrillation, 22.2% large vessel atherosclerosis and 33.3% for small vessel disease trials. Only 19 (5.9%) of the trials had participatory contributions from a country in sub-Saharan Africa (South Africa only). CONCLUSIONS: Compared to their global burden of stroke, LMICs are underrepresented in key clinical trials used in formulating a prominent global stroke prevention guideline. While current therapeutic recommendations are likely applicable to practice settings throughout the world, greater involvement of patients from LMIC settings will enhance the contextual relevance and generalizability of recommendations to these disparate populations.

Polypill Programs to Prevent Stroke and Cut Costs in Low Income Countries: Moving From Clinical Efficacy to Pragmatic Implementation.

Current projections are that the already overwhelming burden of strokes and atherosclerotic cardiovascular diseases in low- and middle-income countries (LMICs) will continue to rise over the coming decades as the prevalence of traditional vascular risk factors burgeon in these countries. Cardiovascular polypills containing combinations of antihypertensive(s), a statin, with or without aspirin or folic acid in the form of a single pill, represent a viable strategy for both primary and secondary prevention of atherosclerotic cardiovascular diseases in LMICs. Large multicenter trials in LMIC and high-income country (HIC) settings have now clearly demonstrated the beneficial effects of the cardiovascular polypill versus placebo (or usual care) in reducing primary stroke risk by 50%. For survivors of a recent myocardial infarction residing in HICs, the polypill reduced risk of major cardiovascular events by 25% due to improved treatment adherence. Data on the clinical efficacy of the polypill for secondary stroke prevention are scanty both in HICs and LMICs. Cost-effectiveness analyses data from LMICs suggest cost savings with the polypill for primary and secondary prevention of stroke and atherosclerotic cardiovascular diseases. However, major contextual barriers in LMICs need to be surmounted through mixed methods research and hybrid clinical trials to assess its real-world effectiveness, before the adoption of the polypill for primary and secondary atherosclerotic cardiovascular disease prevention in routine clinical practice.

Atherosclerotic event risk and risk reduction therapies among Ghanaian hemorrhagic stroke survivors.

BACKGROUND: Intracerebral hemorrhage (ICH) stroke constitute up to 40% of incident strokes in Africa. While ICH patients are at high risk for atherosclerotic events, the risk-benefit of anti-atherosclerotic therapies in this patient population is uncertain. PURPOSE: To assess whether utility of statins and/or antithrombotic agents after surviving an ICH correlates with atherosclerotic risk of an observational cohort. METHODS: We analyzed data in a stroke registry prospectively collected on consecutively encountered stroke survivors seen at an out-patient clinic in Ghana between January 2018 and March 2020. We collected baseline demographic and clinical details, including diagnosis of ICH, co-morbidities, and key atherosclerotic risk reduction therapies (statins and anti-platelet drugs). We computed ischemic vascular risk using the Framingham Risk Score (FRS) to classify patients into low, intermediate and high vascular risk. RESULTS: Of 1101 stroke survivors seen during the period, 244 (22.2%) had ICH. Vascular risk profiles were low (n = 86; 35.2%), intermediate (n = 71; 29.1%) and high (n = 87; 35.7%). Utility of statin use was 76.7% (low risk), 84.5% (intermediate risk), and 87.4% (high risk), p = 0.16 while antiplatelet use trended with atherosclerotic risk being 9.3% (low risk), 25.4% (intermediate risk), and high risk (34.5%), p = 0.0004. Independent factors associated with statin use were hypertension (OR 8.80; 95% CI: 2.34-33.11) and cigarette smoking (OR 0.29; 95% CI: 0.09-0.89) while antiplatelet drug use was associated with age (OR 1.43; 95% CI: 1.06-1.92) and time from index stroke (OR: 1.02; 95% CI: 1.01-1.02). CONCLUSION: Approximately two-thirds of ICH survivors in this African sample had intermediate to high risk of future atherosclerotic events. Clinical trials on the timing, safety, and efficacy of statins and antiplatelet drugs among ICH survivors could help better guide risk mitigation in this population.

Factors Linked to Chronic Kidney Disease Among Stroke Survivors in Ghana.

BACKGROUND: Chronic kidney disease (CKD) is associated with poor outcomes among stroke survivors. In Africa, where both stroke and CKD incidence rates are escalating, little, if anything, is known about the burden of CKD among stroke survivors. OBJECTIVE: To assess the frequency and factors associated with CKD among stroke survivors by primary stroke types. METHODS: Stroke registry data were prospectively collected on consecutively encountered stroke survivors seen at an out-patient clinic in Ghana between January 2018 and March 2020. We calculated estimated glomerular filtration rate (eGFR) using the CKD-EPI formula and defined CKD as eGFR <60ml/min. Factors associated with CKD were assessed using multiple logistic regression modelling. RESULTS: Among 759 stroke survivors, 159 had CKD giving a prevalence of 21.0% (95%CI: 18.1% - 23.8%). The mean age of those with CKD was 61.6 ± 14.2 years compared with 57.5 ± 13.6 years, p=0.0007 among those without CKD. Five factors remained significantly associated with CKD with the following adjusted odds ratio (aOR and 95% CI). Age per decile rise 1.30 (1.13-1.50), male sex 1.99 (1.36-2.93), rural dwelling residence 1.95 (1.06-3.59), prior use of antihypertensive meds before index stroke onset 1.63 (1.08-2.47), and number of antihypertensive medication classes 1.25 (1.06-1.45). CONCLUSION: 1 in 5 stroke survivors have evidence of chronic kidney disease in this Ghanaian study. Targeted interventions focusing on optimizing blood pressure control and rural dwellers may mitigate their risk for adverse outcomes.