Natural history of motor symptoms in Parkinson's disease and the long-duration response to levodopa.

The natural pattern of progression of Parkinson's disease is largely unknown because patients are conventionally followed on treatment. As Parkinson's disease progresses, the true magnitude of the long-duration response to levodopa remains unknown, because it can only be estimated indirectly in treated patients. We aimed to describe the natural course of motor symptoms by assessing the natural OFF in consecutive Parkinson's disease patients never exposed to treatment (drug-naïve), and to investigate the effects of daily levodopa on the progression of motor disability in the OFF medication state over a 2-year period. In this prospective naturalistic study in sub-Saharan Africa, 30 Parkinson's disease patients (age at onset 58 ± 14 years, disease duration 7 ± 4 years) began levodopa monotherapy and were prospectively assessed using the Unified Parkinson's disease Rating Scale (UPDRS). Data were collected at baseline, at 1-year and 2-years follow-up. First-ever levodopa intake induced a significant improvement in motor symptoms (natural OFF versus ON state UPDRS-III 41.9 ± 15.9 versus 26.8 ± 15.1, respectively; P < 0.001). At 1-year follow-up, OFF state UPDRS-III score after overnight withdrawal of levodopa was considerably lower than natural OFF (26.5 ± 14.9; P < 0 .001). This effect was not modified by disease duration. At the 2-year follow-up, motor signs after overnight OFF (30.2 ± 14.2) were still 30% milder than natural OFF (P = 0.001). The ON state UPDRS-III at the first-ever levodopa challenge was similar to the overnight OFF score at 1-year follow-up and the two conditions were correlated (r = 0.72, P < 0.001). Compared to the natural progression of motor disability, levodopa treatment resulted in a 31% lower annual decline in UPDRS-III scores in the OFF state (3.33 versus 2.30 points/year) with a lower model's variance explained by disease duration (67% versus 36%). Using the equation regressed on pretreatment data, we predicted the natural OFF at 1-year and 2-year follow-up visits and estimated that the magnitude of the long-duration response to levodopa ranged between 60% and 65% of total motor benefit provided by levodopa, independently of disease duration (P = 0.13). Although levodopa therapy was associated with motor fluctuations, overnight OFF disability during levodopa was invariably less severe than the natural course of the disease, independently of disease duration. The same applies to the yearly decline in UPDRS-III scores in the OFF state. Further research is needed to clarify the mechanisms underlying the long-duration response to levodopa in Parkinson's disease. Understanding the natural course of Parkinson's disease and the long-duration response to levodopa may help to develop therapeutic strategies increasing its magnitude to improve patient quality of life and to better interpret the outcome of randomized clinical trials on disease-modifying therapies that still rely on the overnight OFF to define Parkinson's disease progression.

Burden and Predictors of Poststroke Cognitive Impairment in a Sample of Ghanaian Stroke Survivors.

BACKGROUND AND OBJECTIVE: There are limited data on vascular cognitive impairment (VCI) from low- and middle-income countries where the stroke burden is burgeoning. The aim of this study was to characterize the burden, determinants, and effects of VCI on health-related quality of life in sub-Saharan Africa (SSA). METHODS: From January 2015 to February 2016, we collected information on 147 consecutive stroke survivors (>45 years) seen at a tertiary hospital in Ghana and 49 demographically matched stroke-free controls. Data collected included demographics, clinical factors, health-related quality of life, and presence of depression. Cognitive status was evaluated using a standard Vascular Neuropsychological Battery that assessed memory, executive function and mental speed, language, and visuospatial-visuoconstructive functioning. Expert VCI guideline and Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition criteria were used to classify stroke patients into no VCI, VCI but no dementia, and vascular dementia (VD). RESULTS: The mean age ± standard deviation of the stroke survivors was 59.9 ± 13.7 years, of which 47.6% were women. Among the cohort, 77 out of 147 (52.3%) had no VCI, 50 of the 147 (34.0%) had VCI without dementia, and 20 of the 147 (13.6%) had VD. Three factors remained significantly associated with VCI: increasing age for each successive 10-year rise (odds ratio [OR] 1.44, 95% confidence interval [CI]: 1.03-2.02), lack of formal education (OR 5.26, 95% CI: 1.01-27.52), and worse functional disability on the modified Rankin scale (OR 2.46, 95% CI: 1.61-3.75). Patients with VD had the poorest health-related quality of life. CONCLUSIONS: Half of the Ghanaian stroke survivors encountered in this cross-sectional study had evidence of cognitive dysfunction. Future studies in SSA will need to identify strategies to address this immense burden.

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.

Neurocysticercosis: A neglected but preventable cause of seizure in adults.

Neurocysticercosis is an infection of the central nervous system caused by the larval stage of Taenia solium. Although endemic in sub-Saharan Africa, it is neglected but remains a significant cause of preventable seizure in adults. Its diagnosis is challenging and is frequently missed due to its variable clinical manifestations and lack of diagnostic facilities in most areas of sub-Saharan Africa. This report discusses two cases of parenchymal neurocysticercosis in Ghanaians who presented to the emergency unit of a District Hospital with adult-onset seizures. The two cases highlight the need for a high index of suspicion and also underscore the important role of neuroimaging in the evaluation of patients presenting with adult-onset seizures in neurocysticercosis endemic areas. This is necessary for prompt detection and initiation of appropriate therapy in order to improve prognosis.

A cardiovascular polypill for secondary stroke prevention in a tertiary centre in Ghana (SMAART): a phase 2 randomised clinical trial.

BACKGROUND: A cardiovascular polypill containing generic drugs might facilitate sustained implementation of and adherence to evidence-based treatments, especially in resource-limited settings. However, the impact of a cardiovascular polypill in mitigating atherosclerotic risk among stroke survivors has not been assessed. We aimed to compare a polypill regimen with usual care on carotid intima-media thickness (CIMT) regression after ischaemic stroke. METHODS: In SMAART, a phase 2 parallel, open-label, assessor-masked, randomised clinical trial, we randomly allocated individuals (aged ≥18 years) who had an ischaemic stroke within the previous 2 months, using a computer-generated randomisation sequence (1:1), to either a polypill or usual care group at a tertiary centre in Ghana. The polypill regimen was a fixed-dose pill containing 5 mg ramipril, 50 mg atenolol, 12·5 mg hydrochlorothiazide, 20 mg simvastatin, and 100 mg aspirin administered as two capsules once per day for 12 months. Usual care was tailored guideline-recommended secondary prevention medications. The primary outcome was the change in CIMT over 12 months with adjustment for baseline values, compared using ANCOVA in all participants with complete data at month 12. Safety was analysed in all randomly assigned participants. This trial is registered at ClinicalTrials.gov, NCT03329599, and is completed. FINDINGS: Between Feb 12, 2019, and Dec 4, 2020, we randomly assigned 148 participants (74 to the usual care group and 74 to the polypill group), 74 (50%) of whom were male and 74 (50%) female. CIMT was assessed in 62 (84%) of 74 participants in the usual care group and 59 (80%) of 74 participants in the polypill group; the main reason for loss to follow-up was participants not completing the study. The mean CIMT change at month 12 was -0·092 mm (95% CI -0·130 to -0·051) in the usual care group versus -0·017 mm (-0·067 to 0·034) in the polypill group, with an adjusted mean difference of 0·049 (-0·008 to 0·109; p=0·11). Serious adverse events occurred among two (3%) participants in the usual care group, and eight (11%) participants in the polypill group (p=0·049). INTERPRETATION: The polypill regimen resulted in similar regression in subclinical atherosclerosis and many secondary and tertiary outcome measures as the tailored drug regimen, but with more serious adverse events. Larger, longer-term, event-based studies, including patients with stroke in primary care settings, are warranted. FUNDING: US National Institutes of Health. TRANSLATION: For the Akan (Twi) translation of the abstract see Supplementary Materials section.

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.

Prevalence and predictors of post-stroke epilepsy among Ghanaian stroke survivors.

BACKGROUND: Post-stroke epilepsy (PSE) is associated with poorer quality of life, higher mortality, and greater health expenditures. We are unaware of any published reports on the frequency of and factors associated with PSE in Africa. PURPOSE: To assess the frequency and factors associated with PSE among Ghanaian stroke survivors. METHODS: We conducted a cross-sectional study of consecutive stroke survivors seen at an out-patient Neurology clinic enrolled into a stroke registry at a tertiary medical center in Ghana between January 2018 and March 2020. We collected baseline demographic and clinical details including diagnosis of post-stroke epilepsy, anti-epileptic medications, presence, treatment and control of vascular risk factors. Multivariate logistic regression models were constructed to identify factors associated with PSE. RESULTS: Of 1101 stroke patients encountered, 126 had PSE (frequency of 11.4%; 95% CI of 9.6-13.5%). Mean (± SD) age among PSE vs. non-PSE patients was 57.7 (± 15.2) vs. 58.7 (± 13.9) years. Factors independently associated with PSE were being male (aOR 1.94; 95% CI: 1.32-2.86), cortical ischemic strokes (1.79; 1.12-2.87), blood pressure > 130/80 mmHg (OR 2.26; 1.06-4.79), use of antihypertensive treatment (OR 0.43; 0.23-0.79). There was an inverted J-shaped curve association between number of classes of antihypertensive drugs prescribed and occurrence of PSE, with the lowest inflection point at 3 classes (OR 0.34; 0.17-0.68). CONCLUSION: In this convenience sample of ambulatory Ghanaian stroke survivors, one in ten had PSE. Further investigations to confirm and clarify the associations between the identified demographic and clinical characteristics are warranted.

Frequency and factors linked to refractory hypertension among stroke survivors in Ghana.

BACKGROUND: Refractory hypertension (RfH) is a rare, severe phenotype of resistant hypertension, linked to higher risk of adverse cardiovascular outcomes. Little is known about the association of RfH with stroke type and subtype. OBJECTIVE: To determine the prevalence and predictors of RfH among stroke survivors in Ghana. METHODS: We interrogated the dataset of a prospectively collected registry of hypertensive patients seen between July 2015 and June 2019, at five hospitals in Ghana. We compared stroke survivors to stroke-free controls. Clinic-based blood pressure was measured using a standardized protocol and antihypertensive medications were assessed via review of medical records and inspection of pills. Refractory hypertension was defined as office BP ≥140/90 mmHg on ≥5 classes of antihypertensive medications. Multivariate logistic regression models were constructed to assess factors associated with RfH. RESULTS: Of 3927 hypertensive patients (1169 stroke survivors, 2758 controls), 86 had RfH for an overall prevalence of 2.2% (95% CI: 1.8-2.7%). Among patients with RfH, 5.8% (4.5-7.3%) were stroke survivors vs. 0.7% (0.4-1.0%) were stroke-free (p < .0001). Adjusted odds ratio (95% CI) for factors associated with RfH were being male (1.81, 1.15-2.85), age < 60 years (2.64, 1.59-4.40), chronic kidney disease (2.09, 1.21-3.60), and known stroke (7.53, 4.35-13.04). RfH was associated with intracerebral hemorrhage, (11.43, 5.65-23.14), ischemic stroke (9.76, 5.47-17.42), lacunar stroke (13.58, 6.45-28.61), and non-lacunar ischemic stroke (3.67, 1.04-13.02). CONCLUSION: Presence of RfH is significantly accentuated among stroke survivors. Intensified efforts are warranted to identify and aggressively address barriers to control in these patients to avert subsequent vascular events.

The dynamics of Poststroke depression among Ghanaians.

OBJECTIVE: The very few published data on post-stroke depression (PSD) among indigenous Africans have covered its prevalence and predictors. We sought to evaluate the dynamics of PSD in a cohort of Ghanaian stroke survivors followed for 9 months after an acute stroke. METHODS: Stroke survivors in this prospective cohort were adults aged >18 years with CT scan confirmed stroke, recruited into a randomized controlled trial to assess the feasibility of an mHealth technology-enabled, nurse guided intervention for blood pressure control. PSD was assessed a secondary outcome measure using the Hamilton Depression Rating Scale (HDRS) at enrollment, months 3, 6, and 9. Those with a score of >7 points on HDRS were categorized as depressed. A multivariate logistic regression analysis was performed to identify independent predictors of PSF. RESULTS: Mean age of study participants was 55.1 ±â€¯12.7 years with 65% being males. Ischemic strokes comprised 76.6% of study population. Prevalence of PSD at baseline was 78.6%, 43.6% at month 3, 41.1% at month 6 and 18.2% at month 9 (p < .0001). Factors significantly associated with PSD at baseline were higher NIH Stoke Scale score (adjusted OR 1.51, 95% CI: 1.03-2.23) and pain (adjusted OR 7.18, 95% CI: 1.52-33.89). NIHSS score (adjusted OR, 1.99, 95% CI: 1.12-3.52) as associated with PSD at month 9. CONCLUSION: 80% Ghanaian stroke survivors have early PSD declining to 20% at month 9. Stroke severity is the persistent factor associated with PSD at baseline and follow-up, and good be a target for screening and promptly treating PSD.

Phone-based intervention for blood pressure control among Ghanaian stroke survivors: A pilot randomized controlled trial.

BACKGROUND: The potential of mobile-health (mHealth) technology for the management of hypertension among stroke survivors in Africa remains unexplored. We assessed whether an mHealth technology-enabled, nurse-guided intervention initiated among stroke patients within one month of symptom onset is effective in improving their blood pressure (BP) control. METHODS: A two-arm pilot cluster randomized controlled trial involving 60 stroke survivors, ≥18 years, with BP ≥140/90 mmHg at screening/enrollment visit at a medical center in Ghana. Participants in the intervention arm (n = 30) received a Blue-toothed BP device and smartphone with an App for monitoring BP measurements and medication intake under nurse guidance for three months after which intervention was withdrawn. Control arm (n = 30) received usual care. Primary outcome measure was proportion with clinic BP < 140/90 mmHg at month 9; secondary outcomes included medication adherence. FINDINGS: Mean ± SD age was 55 ± 13 years, 65% males. Two participants on intervention and three in control group were lost to follow-up. At month 9, proportion on the intervention versus controls with BP < 140/90 mmHg was 14/30 (46.7%) versus 12/30 (40.0%), p = 0.79 by intention-to-treat; systolic BP < 140 mmHg was 22/30 (73.3%) versus 13/30 (43.3%), p = 0.035. Mean ± SD medication possession ratio was 0.95 ± 0.16 on intervention versus 0.98 ± 0.24 in the control arm, p = 0.56. INTERPRETATION: We demonstrate feasibility and signal of improvement in BP control among stroke survivors in a resource-limited setting via an mHealth intervention. Larger scale studies are warranted. TRIAL REGISTRATION: NCT02568137. Registered on 13 July 2015 at ClinicalTrials.gov.

Stroke Minimization through Additive Anti-atherosclerotic Agents in Routine Treatment (SMAART): study protocol for a randomized controlled trial.

BACKGROUND: There is an unprecedented rise in the prevalence of stroke in sub-Saharan Africa (SSA). Secondary prevention guidelines recommend that antihypertensive, statin and antiplatelet therapy be initiated promptly after ischemic stroke and adhered to in a persistent fashion to achieve optimal vascular-risk reduction. However, these goals are seldom realized in routine clinical care settings in SSA due to logistical challenges. We seek to assess whether a polypill containing fixed doses of three antihypertensive agents, a statin and antiplatelet therapy taken once daily per os for 12 months among recent stroke survivors would result in carotid intimal thickness regression compared with usual care (UC). METHODS: The Stroke Minimization through Additive Anti-atherosclerotic Agents in Routine Treatment (SMAART) trial is a phase 2, open-label, evaluator-blinded trial involving 120 Ghanaian recent-ischemic-stroke survivors. Using a computer-generated sequence, patients will be randomly allocated 1:1 into either the intervention arm or UC. Patients in the intervention arm will receive Polycap DS® (containing aspirin, 100 mg; atenolol, 50 mg; ramipril, 5 mg; thiazide, 12.5 mg; simvastatin, 20 mg) taken as two capsules once daily. Patients in the UC will receive separate, individual secondary preventive medications prescribed at the physician's discretion. Both groups will be followed for 12 months to assess changes in carotid intimal thickness regression - a surrogate marker of atherosclerosis - as primary outcome measure. Secondary outcome measures include adherence to therapy, safety and tolerability, health-related quality of life, patient satisfaction, functional status, depression and cognitive dysfunction. DISCUSSION: An efficacy-suggesting SMAART trial could inform the future design of a multi-center, double-blinded, placebo-controlled, parallel-group, randomized controlled trial comparing the clinical efficacy of the polypill strategy for vascular risk moderation among stroke survivors in SSA. TRIAL REGISTRATION: ClinicalTrials.gov , ID: NCT03329599 . Registered on 11 February 2017.