Ramesh Sahathevan

Dementia, stroke, and vascular risk factors; a review.

Interest in dementia has increased over the past few decades. Stroke is an important cause of cognitive problems. The term vascular cognitive impairment is now used to describe dementia attributed to stroke or deep white matter lesions detected on imaging. Although vascular cognitive impairment is increasingly diagnosed, Alzheimers disease remains the most common dementia worldwide. The relationship between Alzheimers disease and vascular cognitive impairment is unclear, although there exists significant overlap, which prompts physicians to consider them opposite ends of a disease spectrum, rather than separate entities. There is also substantial evidence that stroke risk factors such as hypertension, diabetes; lipid disorders, etc. are independently associated with an increased risk of Alzheimers disease and vascular cognitive impairment. Evidence suggests that these risk factors have a cumulative effect on Alzheimers disease development but not on vascular cognitive impairment. This is more marked in Alzheimers disease patients in the presence of the ε4 allelic variant of apolipoprotein E. How these risk factors increase the risk of dementia is largely unknown. Physicians must be aware that stroke causes dementia; that vascular risk factors appear to be independent risk factors in developing dementia, and that poststroke care must include cognitive assessment.

Sex Differences in Stroke Incidence, Prevalence, Mortality and DALYs: Results from the Global Burden of Disease Study 2013

Background: Accurate information on stroke burden in men and women are important for evidence-based healthcare planning and resource allocation. Previously, limited research suggested that the absolute number of deaths from stroke in women was greater than in men, but the incidence and mortality rates were greater in men. However, sex differences in various metrics of stroke burden on a global scale have not been a subject of comprehensive and comparable assessment for most regions of the world, nor have sex differences in stroke burden been examined for trends over time. Methods: Stroke incidence, prevalence, mortality, disability-adjusted life years (DALYs) and healthy years lost due to disability were estimated as part of the Global Burden of Disease (GBD) 2013 Study. Data inputs included all available information on stroke incidence, prevalence and death and case fatality rates. Analysis was performed separately by sex and 5-year age categories for 188 countries. Statistical models were employed to produce globally comprehensive results over time. All rates were age-standardized to a global population and 95% uncertainty intervals (UIs) were computed. Findings: In 2013, global ischemic stroke (IS) and hemorrhagic stroke (HS) incidence (per 100,000) in men (IS 132.77 (95% UI 125.34-142.77); HS 64.89 (95% UI 59.82-68.85)) exceeded those of women (IS 98.85 (95% UI 92.11-106.62); HS 45.48 (95% UI 42.43-48.53)). IS incidence rates were lower in 2013 compared with 1990 rates for both sexes (1990 male IS incidence 147.40 (95% UI 137.87-157.66); 1990 female IS incidence 113.31 (95% UI 103.52-123.40)), but the only significant change in IS incidence was among women. Changes in global HS incidence were not statistically significant for males (1990 = 65.31 (95% UI 61.63-69.0), 2013 = 64.89 (95% UI 59.82-68.85)), but was significant for females (1990 = 64.892 (95% UI 59.82-68.85), 2013 = 45.48 (95% UI 42.427-48.53)). The number of DALYs related to IS rose from 1990 (male = 16.62 (95% UI 13.27-19.62), female = 17.53 (95% UI 14.08-20.33)) to 2013 (male = 25.22 (95% UI 20.57-29.13), female = 22.21 (95% UI 17.71-25.50)). The number of DALYs associated with HS also rose steadily and was higher than DALYs for IS at each time point (male 1990 = 29.91 (95% UI 25.66-34.54), male 2013 = 37.27 (95% UI 32.29-45.12); female 1990 = 26.05 (95% UI 21.70-30.90), female 2013 = 28.18 (95% UI 23.68-33.80)). Interpretation: Globally, men continue to have a higher incidence of IS than women while significant sex differences in the incidence of HS were not observed. The total health loss due to stroke as measured by DALYs was similar for men and women for both stroke subtypes in 2013, with HS higher than IS. Both IS and HS DALYs show an increasing trend for both men and women since 1990, which is statistically significant only for IS among men. Ongoing monitoring of sex differences in the burden of stroke will be needed to determine if disease rates among men and women continue to diverge. Sex disparities related to stroke will have important clinical and policy implications that can guide funding and resource allocation for national, regional and global health programs.

Sleep disturbances in Malaysian patients with Parkinson's disease using polysomnography and PDSS

BACKGROUND Sleep disturbances such as sleep fragmentation, sleep disordered breathing (SDB), periodic limb movements (PLM), excessive daytime somnolence (EDS) and insomnia are prevalent in Parkinsons disease (PD). However, studies in the Asian population are limited. METHODS This was a cross-sectional study involving 46 Malaysians with PD using polysomnography (PSG) and standardized translated Parkinsons disease sleep scale (PDSS). Overnight PSG recordings, UPDRS and PDSS scores, and baseline demographic data were obtained. RESULTS Data from 44 patients were analysed. Thirty-six patients (81.8%) had PSG-quantified sleep disorders. Twenty-three (52.3%) had sleep fragmentation, 24 (54.6%) had SDB and 14 (32%) had PLM. EDS was present in 9.1%. Insomnia was reported by 31.8%. Patients with sleep fragmentation had significantly higher UPDRS scores and lower PDSS insomnia sub-scores. The UPDRS scores correlated negatively with the TST and sleep efficiency. All patients with EDS had SDB (p=0.056). The PDSS insomnia sub-items correlated with sleep fragmentation on PSG. CONCLUSION : The prevalence of sleep disorders based on PSG and PDSS in our PD patients was high, the commonest being sleep fragmentation and SDB, while EDS was the least prevalent. Problem specific sub-items of the PDSS were more accurate in predicting the relevant PSG-related changes compared to the PDSS as a whole.

The Stroke RiskometerTM App: Validation of a data collection tool and stroke risk predictor

Background The greatest potential to reduce the burden of stroke is by primary prevention of first-ever stroke, which constitutes three quarters of all stroke. In addition to population-wide prevention strategies (the ‘mass’ approach), the ‘high risk’ approach aims to identify individuals at risk of stroke and to modify their risk factors, and risk, accordingly. Current methods of assessing and modifying stroke risk are difficult to access and implement by the general population, amongst whom most future strokes will arise. To help reduce the burden of stroke on individuals and the population a new app, the Stroke Riskometer™, has been developed. We aim to explore the validity of the app for predicting the risk of stroke compared with current best methods. Methods 752 stroke outcomes from a sample of 9501 individuals across three countries (New Zealand, Russia and the Netherlands) were utilized to investigate the performance of a novel stroke risk prediction tool algorithm (Stroke Riskometer™) compared with two established stroke risk score prediction algorithms (Framingham Stroke Risk Score [FSRS] and QStroke). We calculated the receiver operating characteristics (ROC) curves and area under the ROC curve (AUROC) with 95% confidence intervals, Harrels C-statistic and D-statistics for measure of discrimination, R2 statistics to indicate level of variability accounted for by each prediction algorithm, the Hosmer-Lemeshow statistic for calibration, and the sensitivity and specificity of each algorithm. Results The Stroke Riskometer™ performed well against the FSRS five-year AUROC for both males (FSRS = 75·0% (95% CI 72·3%–77·6%), Stroke Riskometer™ = 74·0(95% CI 71·3%–76·7%) and females [FSRS = 70·3% (95% CI 67·9%–72·8%, Stroke Riskometer™ = 71·5% (95% CI 69·0%–73·9%)], and better than QStroke [males–59·7% (95% CI 57·3%–62·0%) and comparable to females = 71·1% (95% CI 69·0%–73·1%)]. Discriminative ability of all algorithms was low (C-statistic ranging from 0·51–0·56, D-statistic ranging from 0·01–0·12). Hosmer-Lemeshow illustrated that all of the predicted risk scores were not well calibrated with the observed event data (P < 0·006). Conclusions The Stroke Riskometer™ is comparable in performance for stroke prediction with FSRS and QStroke. All three algorithms performed equally poorly in predicting stroke events. The Stroke Riskometer™ will be continually developed and validated to address the need to improve the current stroke risk scoring systems to more accurately predict stroke, particularly by identifying robust ethnic/race ethnicity group and country specific risk factors.

New Strategy to Reduce the Global Burden of Stroke

The socioeconomic and health effect of stroke and other noncommunicable disorders (NCDs) that share many of the same risk factors with stroke, such as heart attack, dementia, and diabetes mellitus, is huge and increasing.1–4 Collectively, NCDs account for 34.5 million deaths (66% of deaths from all causes)3 and 1344 million disability-adjusted life years lost worldwide in 2010.2 The burden of NCDs is likely to burgeon given the aging of the world’s population and the epidemiological transition currently observed in many low- to middle-income countries (LMICs).5,6 In addition, there is low awareness in the population about these NCDs and their risk factors,7–10 particularly in LMICs.11 These factors, coupled with underuse of strategies for primary prevention of stroke/NCDs on an individual level and the lack of accurate data on the prevalence and effect of risk factors in different countries and populations have been implicated in the ever-increasing worldwide burden of the NCDs.12–15 Of particular concern is a significant increase in the number of young adults (aged <65 years) affected by stroke,16 and the increasing epidemic of overweight/obesity17 and diabetes mellitus worldwide.18 If these trends continue, the burden of stroke and other major NCDs will increase even faster. The increasing burden of stroke and other major NCDs provide strong support for the notion that the currently used primary prevention strategies for stroke and other major NCDs (business as usual) are not sufficiently effective. The most pertinent solution to this problem is the implementation of new, effective, widely available, and cost-effective prevention and treatment strategies to reduce the incidence and severity distribution of stroke and other major NCDs. The recent INTERSTROKE case-control study, conducted in 22 countries worldwide, provided evidence that, collectively, 10 risk factors accounted …

Subacute Ischemic Stroke Is Associated With Focal 11C PiB Positron Emission Tomography Retention But Not With Global Neocortical Aβ Deposition

Background and Purpose— Conflicting evidence exists as to whether focal cerebral ischemia contributes to cerebral amyloid deposition. We aimed to look at A&bgr; deposits, detected by N-methyl-2-(4′-methylaminophenyl)-6-hydroxybenzothiazole (PiB) positron emission tomography, in patients with recent ischemic stroke. Specifically, we hypothesized that patients with recent ischemic stroke have higher local and neocortical PiB positron emission tomography retention and that this may be associated with major vascular risk factors. Methods— Ischemic stroke patients were studied using PiB positron emission tomography within 30 days and compared to age-matched controls. Distribution volume ratio maps were created using Logan graphical analysis with the cerebellar cortex as a reference. Results— Among the 21 ischemic stroke patients (median age, 76 years; interquartile range, 68–77), the ipsilateral peri-infarct region PiB retention was higher compared to the contralateral mirror region, with a PiB distribution volume ratio difference of 0.29 (95% CI, 0.2–0.44; P=0.001) at median 10 (interquartile range, 7–14) days after stroke. Two patients also had higher PiB retention within the infarct compared to the contralateral side. There was no difference in the neocortical PiB retention elsewhere in the brain among ischemic stroke patients compared with 22 age-matched normal controls (P=0.22). Among the risk factors in the ischemic stroke patients, diabetes was associated with a higher neocortical PiB retention (Spearman Rho=0.48; 95% CI, 0.28–0.72). Conclusions— PiB retention was higher in the peri-infarct region among patients with recent ischemic stroke. This did not translate into a higher global neocortical PiB retention except possibly in patients with diabetes. The cause of the focal PiB retention is uncertain and requires further investigation.

Positron Emission Tomographic Imaging in Stroke Cross-Sectional and Follow-Up Assessment of Amyloid in Ischemic Stroke

Background and Purpose— Cardiovascular risk factors significantly increase the risk of developing Alzheimer disease. A possible mechanism may be via ischemic infarction–driving amyloid deposition. We conducted a study to determine the presence of &bgr;-amyloid in infarct, peri-infarct, and hemispheric areas after stroke. We hypothesized that an infarct would trigger &bgr;-amyloid deposition, with deposition over time. Methods— Patients were recruited within 40 days of acute ischemic stroke and imaged with computed tomographic or magnetic resonance imaging and Pittsburgh compound B (11C-PiB) positron emission tomographic scans. Follow-up positron emission tomographic scanning was performed in a subgroup ⩽18 months after the stroke event. Standardized uptake value ratios for regions of interest were analyzed after coregistration. Results— Forty-seven patients were imaged with 11C-PiB positron emission tomography. There was an increase in 11C-PiB accumulation in the stroke area compared with a reference region in the contralesional hemisphere, which was not statistically significant (median difference in standardized uptake value ratio, 0.07 [95% confidence interval, −0.06 to 0.123]; P=0.452). There was no significant increase in the accumulation of 11C-PiB in the peri-infarct region or in the ipsilesional hemisphere (median difference in standardized uptake value ratio, 0.04 [95% confidence interval, −0.02 to 0.10]; P=0.095). We repeated 11C-PiB positron emission tomography in 21 patients and found a significant reduction in accumulation of 11C-PiB between regions of interest (median difference in standardized uptake value ratio, −0.08 [95% confidence interval, −0.23 to −0.03]; P=0.04). Conclusions— There was no significant increase in 11C-PiB accumulation in or around the infarct. There was no increase in ipsilesional hemispheric 11C-PiB accumulation over time. We found no evidence that infarction leads to sustained or increased &bgr;-amyloid deposition ⩽18 months after stroke.

Post-dengue parkinsonism

BackgroundDengue is a common illness in the tropics. Equally common are neurological complications that stem from dengue infection. However, to date, parkinsonism following dengue has not been reported in medical literature.Case presentationA previously well 18-year old man developed parkinsonism, in addition to other neurological symptoms following serologically confirmed dengue fever. Alternative etiologies were excluded by way of imaging and blood investigations.ConclusionsThe authors detail the first reported case of parkinsonism complicating dengue fever. Keeping rare presentations of common illnesses in mind, it behoves clinicians to consider parkinsonism as a complication following dengue infection. This would prevent injudicious treatment with L-dopa and dopamine agonists. Immunosuppression with steroids has been shown to be helpful in certain cases.

A Bahasa Malaysia version of the Montreal Cognitive Assessment: Validation in stroke

BACKGROUND Many stroke research trials do not include assessment of cognitive function. A Very Early Rehabilitation Trial (AVERT) is an international multicenter study that includes the Montreal Cognitive Assessment (MoCA) as an outcome. At the Malaysian AVERT site, completion of the MoCA has been limited by low English proficiency in some participants. We aimed to develop a Bahasa Malaysia (BM) version of the MoCA and to validate it in a stroke population. METHODS The original English version of the MoCA was translated into BM and then back-translated to ensure accuracy. Feasibility testing in a group of stroke patients prompted minor changes to the BM MoCA. In the validation phase, a larger group of bilingual stroke patients completed both the original English MoCA and the finalized BM MoCA, with presentation order counter-balanced. RESULTS Forty stroke patients participated, with a mean age of 57.2 (SD = 10.3). Agreement between BM MoCA and English MoCA was strong (intra-class correlation coefficient = 0.81, 95% CI 0.68-0.90). Scores on BM MoCA were slightly higher than scores on English MoCA (median absolute difference = 2.0, IQR 0-3.5), and this difference was present regardless of which version was completed first. CONCLUSIONS The existence of a validated BM version of the MoCA will be of major benefit to clinicians and researchers in Malaysia and the wider South-east Asian region, where the Malay language is used by over 200 million people.

Strategies to improve stroke care services in low- and middle-income countries: a systematic review.

Background: The burden of stroke in low- and middle-income countries (LMICs) is large and increasing, challenging the already stretched health-care services. Aims and Objectives: To determine the quality of existing stroke-care services in LMICs and to highlight indigenous, inexpensive, evidence-based implementable strategies being used in stroke-care. Methods: A detailed literature search was undertaken using PubMed and Google scholar from January 1966 to October 2015 using a range of search terms. Of 921 publications, 373 papers were shortlisted and 31 articles on existing stroke-services were included. Results: We identified efficient models of ambulance transport and pre-notification. Stroke Units (SU) are available in some countries, but are relatively sparse and mostly provided by the private sector. Very few patients were thrombolysed; this could be increased with telemedicine and governmental subsidies. Adherence to secondary preventive drugs is affected by limited availability and affordability, emphasizing the importance of primary prevention. Training of paramedics, care-givers and nurses in post-stroke care is feasible. Conclusion: In this systematic review, we found several reports on evidence-based implementable stroke services in LMICs. Some strategies are economic, feasible and reproducible but remain untested. Data on their outcomes and sustainability is limited. Further research on implementation of locally and regionally adapted stroke-services and cost-effective secondary prevention programs should be a priority.