The Role of Human Immunodeficiency Virus-Associated Vasculopathy in the Etiology of Stroke.

Background: Human immunodeficiency virus (HIV) infection is a recognized risk factor for stroke among young populations, but the exact mechanisms are poorly understood. We studied the clinical, radiologic, and histologic features of HIV-related ischemic stroke to gain insight into the disease mechanisms. Methods: We conducted a prospective, in-depth analysis of adult ischemic stroke patients presenting to Queen Elizabeth Central Hospital, Blantyre, Malawi, in 2011. Results: We recruited 64 HIV-infected and 107 HIV-uninfected patients. Those with HIV were significantly younger (P < .001) and less likely to have established vascular risk factors. Patients with HIV were more likely to have large artery disease (21% vs 10%; P < .001). The commonest etiology was HIV-associated vasculopathy (24 [38%]), followed by opportunistic infections (16 [25%]). Sixteen of 64 (25%) had a stroke soon after starting antiretroviral therapy (ART), suggesting an immune reconstitution-like syndrome. In this group, CD4+ T-lymphocyte count was low, despite a significantly lower HIV viral load in those recently started on treatment (P < .001). Conclusions: HIV-associated vasculopathy and opportunistic infections are common causes of HIV-related ischemic stroke. Furthermore, subtypes of HIV-associated vasculopathy may manifest as a result of an immune reconstitution-like syndrome after starting ART. A better understanding of this mechanism may point toward new treatments.

Global and regional burden of stroke during 1990-2010: findings from the Global Burden of Disease Study 2010.

BACKGROUND: Although stroke is the second leading cause of death worldwide, no comprehensive and comparable assessment of incidence, prevalence, mortality, disability, and epidemiological trends has been estimated for most regions. We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010) to estimate the global and regional burden of stroke during 1990-2010. METHODS: We searched Medline, Embase, LILACS, Scopus, PubMed, Science Direct, Global Health Database, the WHO library, and WHO regional databases from 1990 to 2012 to identify relevant studies published between 1990 and 2010.We applied the GBD 2010 analytical technique (DisMod-MR), based on disease-specific, pre-specified associations between incidence, prevalence, and mortality, to calculate regional and country-specific estimates of stroke incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) lost by age group (<75 years, ≥ 75 years, and in total)and country income level (high-income, and low-income and middle-income) for 1990, 2005, and 2010. FINDINGS: We included 119 studies (58 from high-income countries and 61 from low-income and middle-income countries). From 1990 to 2010, the age-standardised incidence of stroke significantly decreased by 12% (95% CI 6-17)in high-income countries, and increased by 12% (-3 to 22) in low-income and middle-income countries, albeit nonsignificantly. Mortality rates decreased significantly in both high income (37%, 31-41) and low-income and middle income countries (20%, 15-30). In 2010, the absolute numbers of people with fi rst stroke (16・9 million), stroke survivors (33 million), stroke-related deaths (5・9 million), and DALYs lost (102 million) were high and had significantly increased since 1990 (68%, 84%, 26%, and 12% increase, respectively), with most of the burden (68・6% incident strokes, 52・2% prevalent strokes, 70・9% stroke deaths, and 77・7% DALYs lost) in low-income and middle-income countries. In 2010, 5・2 million (31%) strokes were in children (aged <20 years old) and young and middle-aged adults(20-64 years), to which children and young and middle-aged adults from low-income and middle-income countries contributed almost 74 000 (89%) and 4・0 million (78%), respectively, of the burden. Additionally, we noted significant geographical differences of between three and ten times in stroke burden between GBD regions and countries. More than 62% of new strokes, 69・8% of prevalent strokes, 45・5% of deaths from stroke, and 71・7% of DALYs lost because of stroke were in people younger than 75 years. INTERPRETATION: Although age-standardised rates of stroke mortality have decreased worldwide in the past two decades,the absolute number of people who have a stroke every year, stroke survivors, related deaths, and the overall global burden of stroke (DALYs lost) are great and increasing. Further study is needed to improve understanding of stroke determinants and burden worldwide, and to establish causes of disparities and changes in trends in stroke burden between countries of different income levels. FUNDING: Bill & Melinda Gates Foundation.

Clinical features, proximate causes, and consequences of active convulsive epilepsy in Africa.

PURPOSE: Epilepsy is common in sub-Saharan Africa (SSA), but the clinical features and consequences are poorly characterized. Most studies are hospital-based, and few studies have compared different ecological sites in SSA. We described active convulsive epilepsy (ACE) identified in cross-sectional community-based surveys in SSA, to understand the proximate causes, features, and consequences. METHODS: We performed a detailed clinical and neurophysiologic description of ACE cases identified from a community survey of 584,586 people using medical history, neurologic examination, and electroencephalography (EEG) data from five sites in Africa: South Africa; Tanzania; Uganda; Kenya; and Ghana. The cases were examined by clinicians to discover risk factors, clinical features, and consequences of epilepsy. We used logistic regression to determine the epilepsy factors associated with medical comorbidities. KEY FINDINGS: Half (51%) of the 2,170 people with ACE were children and 69% of seizures began in childhood. Focal features (EEG, seizure types, and neurologic deficits) were present in 58% of ACE cases, and these varied significantly with site. Status epilepticus occurred in 25% of people with ACE. Only 36% received antiepileptic drugs (phenobarbital was the most common drug [95%]), and the proportion varied significantly with the site. Proximate causes of ACE were adverse perinatal events (11%) for onset of seizures before 18 years; and acute encephalopathy (10%) and head injury prior to seizure onset (3%). Important comorbidities were malnutrition (15%), cognitive impairment (23%), and neurologic deficits (15%). The consequences of ACE were burns (16%), head injuries (postseizure) (1%), lack of education (43%), and being unmarried (67%) or unemployed (57%) in adults, all significantly more common than in those without epilepsy. SIGNIFICANCE: There were significant differences in the comorbidities across sites. Focal features are common in ACE, suggesting identifiable and preventable causes. Malnutrition and cognitive and neurologic deficits are common in people with ACE and should be integrated into the management of epilepsy in this region. Consequences of epilepsy such as burns, lack of education, poor marriage prospects, and unemployment need to be addressed.

Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010.

BACKGROUND: Reliable and timely information on the leading causes of death in populations, and how these are changing, is a crucial input into health policy debates. In the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010), we aimed to estimate annual deaths for the world and 21 regions between 1980 and 2010 for 235 causes, with uncertainty intervals (UIs), separately by age and sex. METHODS: We attempted to identify all available data on causes of death for 187 countries from 1980 to 2010 from vital registration, verbal autopsy, mortality surveillance, censuses, surveys, hospitals, police records, and mortuaries. We assessed data quality for completeness, diagnostic accuracy, missing data, stochastic variations, and probable causes of death. We applied six different modelling strategies to estimate cause-specific mortality trends depending on the strength of the data. For 133 causes and three special aggregates we used the Cause of Death Ensemble model (CODEm) approach, which uses four families of statistical models testing a large set of different models using different permutations of covariates. Model ensembles were developed from these component models. We assessed model performance with rigorous out-of-sample testing of prediction error and the validity of 95% UIs. For 13 causes with low observed numbers of deaths, we developed negative binomial models with plausible covariates. For 27 causes for which death is rare, we modelled the higher level cause in the cause hierarchy of the GBD 2010 and then allocated deaths across component causes proportionately, estimated from all available data in the database. For selected causes (African trypanosomiasis, congenital syphilis, whooping cough, measles, typhoid and parathyroid, leishmaniasis, acute hepatitis E, and HIV/AIDS), we used natural history models based on information on incidence, prevalence, and case-fatality. We separately estimated cause fractions by aetiology for diarrhoea, lower respiratory infections, and meningitis, as well as disaggregations by subcause for chronic kidney disease, maternal disorders, cirrhosis, and liver cancer. For deaths due to collective violence and natural disasters, we used mortality shock regressions. For every cause, we estimated 95% UIs that captured both parameter estimation uncertainty and uncertainty due to model specification where CODEm was used. We constrained cause-specific fractions within every age-sex group to sum to total mortality based on draws from the uncertainty distributions. FINDINGS: In 2010, there were 52·8 million deaths globally. At the most aggregate level, communicable, maternal, neonatal, and nutritional causes were 24·9% of deaths worldwide in 2010, down from 15·9 million (34·1%) of 46·5 million in 1990. This decrease was largely due to decreases in mortality from diarrhoeal disease (from 2·5 to 1·4 million), lower respiratory infections (from 3·4 to 2·8 million), neonatal disorders (from 3·1 to 2·2 million), measles (from 0·63 to 0·13 million), and tetanus (from 0·27 to 0·06 million). Deaths from HIV/AIDS increased from 0·30 million in 1990 to 1·5 million in 2010, reaching a peak of 1·7 million in 2006. Malaria mortality also rose by an estimated 19·9% since 1990 to 1·17 million deaths in 2010. Tuberculosis killed 1·2 million people in 2010. Deaths from non-communicable diseases rose by just under 8 million between 1990 and 2010, accounting for two of every three deaths (34·5 million) worldwide by 2010. 8 million people died from cancer in 2010, 38% more than two decades ago; of these, 1·5 million (19%) were from trachea, bronchus, and lung cancer. Ischaemic heart disease and stroke collectively killed 12·9 million people in 2010, or one in four deaths worldwide, compared with one in five in 1990; 1·3 million deaths were due to diabetes, twice as many as in 1990. The fraction of global deaths due to injuries (5·1 million deaths) was marginally higher in 2010 (9·6%) compared with two decades earlier (8·8%). This was driven by a 46% rise in deaths worldwide due to road traffic accidents (1·3 million in 2010) and a rise in deaths from falls. Ischaemic heart disease, stroke, chronic obstructive pulmonary disease (COPD), lower respiratory infections, lung cancer, and HIV/AIDS were the leading causes of death in 2010. Ischaemic heart disease, lower respiratory infections, stroke, diarrhoeal disease, malaria, and HIV/AIDS were the leading causes of years of life lost due to premature mortality (YLLs) in 2010, similar to what was estimated for 1990, except for HIV/AIDS and preterm birth complications. YLLs from lower respiratory infections and diarrhoea decreased by 45-54% since 1990; ischaemic heart disease and stroke YLLs increased by 17-28%. Regional variations in leading causes of death were substantial. Communicable, maternal, neonatal, and nutritional causes still accounted for 76% of premature mortality in sub-Saharan Africa in 2010. Age standardised death rates from some key disorders rose (HIV/AIDS, Alzheimer's disease, diabetes mellitus, and chronic kidney disease in particular), but for most diseases, death rates fell in the past two decades; including major vascular diseases, COPD, most forms of cancer, liver cirrhosis, and maternal disorders. For other conditions, notably malaria, prostate cancer, and injuries, little change was noted. INTERPRETATION: Population growth, increased average age of the world's population, and largely decreasing age-specific, sex-specific, and cause-specific death rates combine to drive a broad shift from communicable, maternal, neonatal, and nutritional causes towards non-communicable diseases. Nevertheless, communicable, maternal, neonatal, and nutritional causes remain the dominant causes of YLLs in sub-Saharan Africa. Overlaid on this general pattern of the epidemiological transition, marked regional variation exists in many causes, such as interpersonal violence, suicide, liver cancer, diabetes, cirrhosis, Chagas disease, African trypanosomiasis, melanoma, and others. Regional heterogeneity highlights the importance of sound epidemiological assessments of the causes of death on a regular basis. FUNDING: Bill & Melinda Gates Foundation.

Differences in the nature of stroke in a multiethnic urban South African population: the Johannesburg hospital stroke register.

BACKGROUND AND PURPOSE: The burden of stroke is increasing in Sub-Saharan Africa (SSA) as the population undergoes epidemiological and demographic transition. Little is known about the nature (risk factors, stroke type and subtype, and causes) of stroke in SSA and whether it differs from stroke in high-income populations. We aimed to compare the nature of stroke between black and white populations in South Africa. METHODS: We used overlapping sources to ascertain consecutive first-ever-in-a-lifetime stroke patients admitted to Johannesburg Hospital over 23 months. We assessed each patient's demographic details, risk factors, CT confirmed pathological stroke type, ischemic stroke subtype and stroke severity, and compared the nature of stroke between black and white stroke patients. RESULTS: 524 patients with presumed stroke were referred. Of these, 432 were first-ever strokes; 308 patients were black and 76 white. Black patients were significantly younger (mean age 51) than white patients (61). Stroke severity was similar (median NIH stroke score 10; 95% CI 8 to 11). More black than white patients had cerebral hemorrhage (27% versus 15%), lacunar stroke (28% versus 22%) and total anterior circulation infarcts (28% versus 22%). Large vessel atherosclerosis (none detected) and ischemic heart disease were very uncommon (1%) as a cause of stroke in black patients. Hypertension (70% versus 68%) and diabetes (14 versus 15%) were as common in black and white stroke patients, but mean cholesterol levels were lower (4.6 mmol/L; 95% CI 4.3 to 4.9 versus 5.3 mmol/L; 4.8 to 5.7) and cigarette smoking less frequent in black patients (23 versus 54%). CONCLUSIONS: Although this was a hospital-based study, the difference in the nature of stroke between black and white stroke patients likely reflects the profile of stroke risk factors. There is an opportunity to prevent an otherwise inevitable increase in atherosclerotic stroke (and IHD) by targeting dietary and smoking habits in the black South African population.

Accuracy of the Siriraj and Guy's Hospital Stroke Scores in urban South Africans.

BACKGROUND AND PURPOSE: The burden of stroke in sub-Saharan Africa is already high and likely to increase, but few patients with stroke have access to brain imaging. Distinguishing pathologic stroke types is relevant both for clinical management and epidemiologic studies. We assessed the accuracy of two stroke scores in distinguishing stroke types in a population known to have a high prevalence of intracranial hemorrhage but low prevalence of atherosclerosis and compared them with the clinicians' assessment of stroke type with computed tomography brain scanning as the "gold standard." METHODS: We assessed the stroke scores and the clinicians' blind assessment of pathologic stroke type in consecutive black patients with stroke included in the Johannesburg Hospital Stroke Register over 23 months. We calculated the accuracy of the scores and clinicians compared with computed tomography brain scan (sensitivity, specificity, positive predictive value, likelihood ratio, kappa statistic). RESULTS: Two hundred twenty-two patients were scanned and assessed within 15 days. Sixty-two (28%) had cerebral hemorrhage and nine (4%) subarachnoid hemorrhage. Neither the Siriraj (sub-Saharan Africa) nor Guy's Hospital score was accurate or offered much advantage over clinician assessment (sensitivity 0.60 and 0.34, specificity 0.88 and 0.95 for intracranial hemorrhage in the Siriraj Stroke Score and Guy's Hospital Stroke Score, respectively; sensitivity 0.70 and 0.71, specificity 0.84 and 0.74, respectively, for ischemic stroke). Although the scores were more accurate when we used new cutoff points, they then failed to diagnose over 80% of stroke types. CONCLUSIONS: The Siriraj Stroke Score and Guy's Hospital Stroke Score are not sufficiently accurate for use in either epidemiologic studies or to guide clinical management in sub-Saharan Africa at present.

Burden of stroke in black populations in sub-Saharan Africa.

Sub-Saharan Africa is undergoing epidemiological transition. Stroke and other vascular diseases increasingly contribute to the burden of disease. There are no systematic reviews of stroke mortality, prevalence, incidence, and case fatality. We combined a thorough search and critical assessment of the published research. Stroke mortality is as high, perhaps higher, than in high-income regions and increases with age in sub-Saharan Africa as in high-income countries, but the absolute number of stroke deaths remains low. There are no adequate community-based stroke incidence studies. Hospital-based incidence is lower than in high-income regions, but higher in young people, possibly due to hospital admission bias. There are no community-based data on case fatality, but hospital-based case fatality is higher than elsewhere. The prevalence of stroke is lower than in high-income regions, but disabling stroke is as prevalent. As the region develops economically, the incidence of stroke and other vascular diseases will increase unless interventions are implemented. Only community-based incidence studies will accurately reveal the burden of stroke.

A cross-sectional study of vascular risk factors in a rural South African population: data from the Southern African Stroke Prevention Initiative (SASPI).

BACKGROUND: Rural sub-Saharan Africa is at an early stage of economic and health transition. It is predicted that the 21st century will see a serious added economic burden from non-communicable disease including vascular disease in low-income countries as they progress through the transition. The stage of vascular disease in a population is thought to result from the prevalence of vascular risk factors. Already hypertension and stroke are common in adults in sub-Saharan Africa. Using a multidisciplinary approach we aimed to assess the prevalence of several vascular risk factors in Agincourt, a rural demographic surveillance site in South Africa. METHODS: We performed a cross sectional random sample survey of adults aged over 35 in Agincourt (population approximately 70 000). Participants were visited at home by a trained nurse who administered a questionnaire, carried out clinical measurements and took a blood sample. From this we assessed participants' history of vascular risk, blood pressure using an OMRON 705 CP monitor, waist circumference, body mass index (BMI), ankle brachial index (ABI), and total and HDL cholesterol. RESULTS: 402 people (24% men) participated. There was a high prevalence of smoking in men, but the number of cigarettes smoked was small. There was a striking difference in mean BMI between men and women (22.8 kg/m2 versus 27.2 kg/m2), but levels of blood pressure were very similar. 43% of participants had a blood pressure greater than 140/90 or were on anti-hypertensive treatment and 37% of participants identified with measured high blood pressure were on pharmacological treatment. 12% of participants had an ABI of < 0.9, sugesting the presence of sub-clinical atheroma. 25.6% of participants had a total cholesterol level > 5 mmol/l. CONCLUSION: We found a high prevalence of hypertension, obesity in women, and a suggestion of subclinical atheroma despite relatively favourable cholesterol levels in a rural South African population. South Africa is facing the challenge of an emerging epidemic of vascular disease. Research to establish the social determinates of these risk factors and interventions to reduce both individual and population risk are required.

Understanding and managing hypertension in an African sub-district: a multidisciplinary approach.

AIMS: To use a multidisciplinary approach to describe the prevalence, lay beliefs, health impact, and treatment of hypertension in the Agincourt sub-district. METHODS: A multidisciplinary team used a range of methods including a cross-sectional random sample survey of vascular risk factors in adults aged 35 years and older, and rapid ethnographic assessment. People who had suffered a stroke were identified by a screening questionnaire followed by a detailed history and examination by a clinician to confirm the likely diagnosis of stroke. Workshops were held for nurses working in the local clinics and an audit of blood pressure measuring devices was carried out. RESULTS: Some 43% of the population 35 and over had hypertension. There was no relationship with gender but a strong positive relationship with age. Illnesses were classified by the population as being either African, with personal or social causes, or White/Western, with physical causes. The causes of hypertension were stated to be both physical and social. Main sources of treatment were the clinics and hospitals but people also sought help from churches and traditional healers. Some 84% of stroke survivors had evidence of hypertension. Few people received treatment for hypertension, although good levels of control were achieved in some. Barriers to providing effective treatment included unreliable drug supply and unreliable equipment to measure blood pressure. CONCLUSIONS: Hypertension is a major problem among older people in Agincourt. There is potential for effective secondary prevention. The potential for primary prevention is less clear. Further information on diet is required.

A Systematic Review of the Huntington Disease-Like 2 Phenotype.

BACKGROUND: Huntington Disease-like 2 (HDL2) is a neurodegenerative disorder similar to Huntington Disease (HD) in its clinical phenotype, genetic characteristics, neuropathology and longitudinal progression. Proposed specific differences include an exclusive African ancestry, lack of eye movement abnormalities, increased Parkinsonism, and acanthocytes in HDL2. OBJECTIVE: The objective was to determine the similarities and differences between HD and HDL2 by establishing the clinical phenotype of HDL2 with the published cases. METHODS: A literature review of all clinically described cases of HDL2 until the end of 2016 was performed and a descriptive analysis was carried out. RESULTS: Sixty-nine new cases were described between 2001 and 2016. All cases had likely African ancestry, and most were found in South Africa and the USA. Many features were found to be similar to HD, including a strong negative correlation between repeat length and age of onset. Chorea was noted in 48/57 cases (84%). Dementia was reported in 74% patients, and Parkinsonism in 37%. Psychiatric features were reported in 44 out of 47 cases. Patients with chorea had lower expanded repeat lengths compared to patients without chorea. Eye movements were described in 19 cases, 8 were abnormal. Acanthocytes were detected in 4 of the 13 patients tested. Nineteen out of 20 MRIs were reported as abnormal with findings similar to HD. CONCLUSION: This review clarifies some aspects of the HDL2 phenotype and highlights others which require further investigation. Features that are unique to HDL2 have been documented in a minority of subjects and require prospective validation.

Use of applied theatre in health research dissemination and data validation: a pilot study from South Africa.

This article reports on a pilot study of the use of applied theatre in the dissemination of health research findings and validation of data. The study took place in South Africa, as part of the Southern Africa Stroke Prevention Initiative (SASPI) and was based at the University/Medical Research Council Rural Public Health and Health Transitions Research Unit (also known as the Agincourt Unit). The aim of SASPI was to investigate the prevalence of stroke and understand the social context of stroke. It was decided to use an applied theatre approach for validating the data and disseminating findings from the anthropological component of the study. The pilot study found that applied theatre worked better in smaller community groups. It allowed data validation and it elicited ideas for future interventions resulting from the health research findings. Evaluation methods of the impact of applied theatre as a vehicle for the dissemination and communication of research findings require further development.

HIV, antiretroviral treatment, hypertension, and stroke in Malawian adults: A case-control study.

OBJECTIVE: To investigate HIV, its treatment, and hypertension as stroke risk factors in Malawian adults. METHODS: We performed a case-control study of 222 adults with acute stroke, confirmed by MRI in 86%, and 503 population controls, frequency-matched for age, sex, and place of residence, using Global Positioning System for random selection. Multivariate logistic regression models were used for case-control comparisons. RESULTS: HIV infection (population attributable fraction [PAF] 15%) and hypertension (PAF 46%) were strongly linked to stroke. HIV was the predominant risk factor for young stroke (≤45 years), with a prevalence of 67% and an adjusted odds ratio (aOR) (95% confidence interval) of 5.57 (2.43-12.8) (PAF 42%). There was an increased risk of a stroke in patients with untreated HIV infection (aOR 4.48 [2.44-8.24], p < 0.001), but the highest risk was in the first 6 months after starting antiretroviral therapy (ART) (aOR 15.6 [4.21-46.6], p < 0.001); this group had a lower median CD4(+) T-lymphocyte count (92 vs 375 cells/mm(3), p = 0.004). In older participants (HIV prevalence 17%), HIV was associated with stroke, but with a lower PAF than hypertension (5% vs 68%). There was no interaction between HIV and hypertension on stroke risk. CONCLUSIONS: In a population with high HIV prevalence, where stroke incidence is increasing, we have shown that HIV is an important risk factor. Early ART use in immunosuppressed patients poses an additional and potentially treatable stroke risk. Immune reconstitution inflammatory syndrome may be contributing to the disease mechanisms.

Arterial ischemic stroke in HIV: Defining and classifying etiology for research studies.

HIV infection, and potentially its treatment, increases the risk of an arterial ischemic stroke. Multiple etiologies and lack of clear case definitions inhibit progress in this field. Several etiologies, many treatable, are relevant to HIV-related stroke. To fully understand the mechanisms and the terminology used, a robust classification algorithm to help ascribe the various etiologies is needed. This consensus paper considers the strengths and limitations of current case definitions in the context of HIV infection. The case definitions for the major etiologies in HIV-related strokes were refined (e.g., varicella zoster vasculopathy and antiphospholipid syndrome) and in some instances new case definitions were described (e.g., HIV-associated vasculopathy). These case definitions provided a framework for an algorithm to help assign a final diagnosis, and help classify the subtypes of HIV etiology in ischemic stroke.

Incidence, Remission and Mortality of Convulsive Epilepsy in Rural Northeast South Africa.

BACKGROUND: Epilepsy is one of the most common neurological conditions globally, estimated to constitute 0.75% of the global burden of disease, with the majority of this burden found in low- and middle- income countries (LMICs). Few studies from LMICs, including much of sub-Saharan Africa, have described the incidence, remission or mortality rates due to epilepsy, which are needed to quantify the burden and inform policy. This study investigates the epidemiological parameters of convulsive epilepsy within a context of high HIV prevalence and an emerging burden of cardiovascular disease. METHODS: A cross-sectional population survey of 82,818 individuals, in the Agincourt Health and Socio-demographic Surveillance Site (HDSS) in rural northeast South Africa was conducted in 2008, from which 296 people were identified with active convulsive epilepsy. A follow-up survey was conducted in 2012. Incidence and mortality rates were estimated, with duration and remission rates calculated using the DISMOD II software package. RESULTS: The crude incidence for convulsive epilepsy was 17.4/100,000 per year (95%CI: 13.1-23.0). Remission was 4.6% and 3.9% per year for males and females, respectively. The standardized mortality ratio was 2.6 (95%CI: 1.7-3.5), with 33.3% of deaths directly related to epilepsy. Mortality was higher in men than women (adjusted rate ratio (aRR) 2.6 (95%CI: 1.2-5.4)), and was significantly associated with older ages (50+ years versus those 0-5 years old (RR 4.8 (95%CI: 0.6-36.4)). CONCLUSIONS: The crude incidence was lower whilst mortality rates were similar to other African studies; however, this study found higher mortality amongst older males. Efforts aimed at further understanding what causes epilepsy in older people and developing interventions to reduce prolonged seizures are likely to reduce the overall burden of ACE in rural South Africa.

Prevalence and risk factors for active convulsive epilepsy in rural northeast South Africa.

RATIONALE: Epilepsy is among the most common neurological disorders worldwide. However, there are few large, population-based studies of the prevalence and risk factors for epilepsy in southern Africa. METHODS: From August 2008 to February 2009, as part of a multi-site study, we undertook a three-stage, population-based study, embedded within the Agincourt health and socio-demographic surveillance system, to estimate the prevalence and identify risk factors of active convulsive epilepsy (ACE) in a rural South African population. RESULTS: The crude prevalence of ACE, after adjusting for non-response and the sensitivity of the screening method, was 7.0/1,000 individuals (95% CI 6.4-7.6) with significant geographic heterogeneity across the study area. Being male (OR=2.3; 95% CI 1.6-3.2), family history of seizures (OR=4.0; 95% CI 2.0-8.1), a sibling with seizures (OR=7.0; 95% CI 1.6-31.7), problems after delivery (OR=5.9; 95% CI 1.2-24.6), and history of snoring (OR=6.5; 95% CI 4.5-9.5) were significantly associated with ACE. For children, their mother's exposure to some formal schooling was protective (OR=0.30; 95% CI 0.11-0.84) after controlling for age and sex. Human immunodeficiency virus was not found to be associated with ACE. CONCLUSIONS: ACE is less frequent in this part of rural South Africa than other parts of sub-Saharan Africa. Improving obstetric services could prevent epilepsy. The relationship between snoring and ACE requires further investigation, as does the relative contribution of genetic and environmental factors to examine the increased risk in those with a family history of epilepsy.

The global burden of hemorrhagic stroke: a summary of findings from the GBD 2010 study.

This report summarizes the findings of the GBD 2010 (Global Burden of Diseases, Injuries, and Risk Factors) study for hemorrhagic stroke (HS). Multiple databases were searched for relevant studies published between 1990 and 2010. The GBD 2010 study provided standardized estimates of the incidence, mortality, mortality-to-incidence ratios (MIR), and disability-adjusted life years (DALY) lost for HS (including intracerebral hemorrhage and subarachnoid hemorrhage) by age, sex, and income level (high-income countries [HIC]; low- and middle-income countries [LMIC]) for 21 GBD 2010 regions in 1990, 2005, and 2010. In 2010, there were 5.3 million cases of HS and over 3.0 million deaths due to HS. There was a 47% increase worldwide in the absolute number of HS cases. The largest proportion of HS incident cases (80%) and deaths (63%) occurred in LMIC countries. There were 62.8 million DALY lost (86% in LMIC) due to HS. The overall age-standardized incidence rate of HS per 100,000 person-years in 2010 was 48.41 (95% confidence interval [CI]: 45.44 to 52.13) in HIC and 99.43 (95% CI: 85.37 to 116.28) in LMIC, and 81.52 (95% CI: 72.27 to 92.82) globally. The age-standardized incidence of HS increased by 18.5% worldwide between 1990 and 2010. In HIC, there was a reduction in incidence of HS by 8% (95% CI: 1% to 15%), mortality by 38% (95% CI: 32% to 43%), DALY by 39% (95% CI: 32% to 44%), and MIR by 27% (95% CI: 19% to 35%) in the last 2 decades. In LMIC countries, there was a significant increase in the incidence of HS by 22% (95% CI: 5% to 30%), whereas there was a significant reduction in mortality rates of 23% (95% CI: -3% to 36%), DALY lost of 25% (95% CI: 7% to 38%), and MIR by 36% (95% CI: 16% to 49%). There were significant regional differences in incidence rates of HS, with the highest rates in LMIC regions such as sub-Saharan Africa and East Asia, and lowest rates in High Income North America and Western Europe. The worldwide burden of HS has increased over the last 2 decades in terms of absolute numbers of HS incident events. The majority of the burden of HS is borne by LMIC. Rates for HS incidence, mortality, and DALY lost, as well as MIR decreased in the past 2 decades in HIC, but increased significantly in LMIC countries, particularly in those patients ≤75 years. HS affected people at a younger age in LMIC than in HIC. The lowest incidence and mortality rates in 2010 were in High Income North America, Australasia, and Western Europe, whereas the highest rates were in Central Asia, Southeast Asia, and sub-Saharan Africa. These results suggest that reducing the burden of HS is a priority particularly in LMIC. The GBD 2010 findings may be a useful resource for planning strategies to reduce the global burden of HS.

The global burden of ischemic stroke: findings of the GBD 2010 study.

This study sought to summarize the findings of the GBD 2010 (Global Burden of Diseases, Injuries, and Risk Factors) study for ischemic stroke (IS) and to report the impact of tobacco smoking on IS burden in specific countries. The GBD 2010 searched multiple databases to identify relevant studies published between 1990 and 2010. The GBD 2010 analytical tools were used to calculate region-specific IS incidence, mortality, mortality-to-incidence ratio, and disability-adjusted life years (DALY) lost, including 95% uncertainty intervals (UI). In 2010, there were approximately 11,569,000 incident IS events (63% in low- and middle-income countries [LMIC]), approximately 2,835,000 deaths from IS (57% in LMIC), and approximately 39,389,000 DALY lost due to IS (64% in LMIC). From 1990 to 2010, there was a significant increase in global IS burden in terms of absolute number of people with incident IS (37% increase), deaths from IS (21% increase), and DALY lost due to IS (18% increase). Age-standardized IS incidence, DALY lost, mortality, and mortality-to-incidence ratios in high-income countries declined by about 13% (95% UI: 6% to 18%), 34% (95% UI: 16% to 36%), and 37% (95% UI: 19% to 39%), 21% (95% UI: 10% to 27%), respectively. However, in LMIC there was a modest 6% increase in the age-standardized incidence of IS (95% UI: -7% to 18%) despite modest reductions in mortality rates, DALY lost, and mortality-to-incidence ratios. There was considerable variability among country-specific estimates within broad GBD regions. China, Russia, and India were ranked highest in both 1990 and 2010 for IS deaths attributable to tobacco consumption. Although age-standardized IS mortality rates have declined over the last 2 decades, the absolute global burden of IS is increasing, with the bulk of DALY lost in LMIC. Tobacco consumption is an important modifiable risk factor for IS, and in both 1990 and 2010, the top ranked countries for IS deaths that could be attributed to tobacco consumption were China, Russia, and India. Tobacco control policies that target both smoking initiation and smoking cessation can play an important role in the prevention of IS. In China, Russia, and India, even modest reductions in the number of current smokers could see millions of lives saved due to prevention of IS alone.

Global and regional burden of first-ever ischaemic and haemorrhagic stroke during 1990-2010: findings from the Global Burden of Disease Study 2010.

BACKGROUND: The burden of ischaemic and haemorrhagic stroke varies between regions and over time. With differences in prognosis, prevalence of risk factors, and treatment strategies, knowledge of stroke pathological type is important for targeted region-specific health-care planning for stroke and could inform priorities for type-specific prevention strategies. We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010) to estimate the global and regional burden of first-ever ischaemic and haemorrhagic stroke during 1990-2010. METHODS: We searched Medline, Embase, LILACS, Scopus, PubMed, Science Direct, Global Health Database, the WHO library, and regional databases from 1990 to 2012 to identify relevant studies published between 1990 and 2010. We applied the GBD 2010 analytical technique (DisMod-MR) to calculate regional and country-specific estimates for ischaemic and haemorrhagic stroke incidence, mortality, mortality-to-incidence ratio, and disability-adjusted life-years (DALYs) lost, by age group (aged <75 years, ≥ 75 years, and in total) and country income level (high-income and low-income and middle-income) for 1990, 2005, and 2010. FINDINGS: We included 119 studies (58 from high-income countries and 61 from low-income and middle-income countries). Worldwide, the burden of ischaemic and haemorrhagic stroke increased significantly between 1990 and 2010 in terms of the absolute number of people with incident ischaemic and haemorrhagic stroke (37% and 47% increase, respectively), number of deaths (21% and 20% increase), and DALYs lost (18% and 14% increase). In the past two decades in high-income countries, incidence of ischaemic stroke reduced significantly by 13% (95% CI 6-18), mortality by 37% (19-39), DALYs lost by 34% (16-36), and mortality-to-incidence ratios by 21% (10-27). For haemorrhagic stroke, incidence reduced significantly by 19% (1-15), mortality by 38% (32-43), DALYs lost by 39% (32-44), and mortality-to-incidence ratios by 27% (19-35). By contrast, in low-income and middle-income countries, we noted a significant increase of 22% (5-30) in incidence of haemorrhagic stroke and a 6% (-7 to 18) non-significant increase in the incidence of ischaemic stroke. Mortality rates for ischaemic stroke fell by 14% (9-19), DALYs lost by 17% (-11 to 21%), and mortality-to-incidence ratios by 16% (-12 to 22). For haemorrhagic stroke in low-income and middle-income countries, mortality rates reduced by 23% (-18 to 25%), DALYs lost by 25% (-21 to 28), and mortality-to-incidence ratios by 36% (-34 to 28). INTERPRETATION: Although age-standardised mortality rates for ischaemic and haemorrhagic stroke have decreased in the past two decades, the absolute number of people who have these stroke types annually, and the number with related deaths and DALYs lost, is increasing, with most of the burden in low-income and middle-income countries. Further study is needed in these countries to identify which subgroups of the population are at greatest risk and who could be targeted for preventive efforts.