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Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World 10 Stroke DEFINITION A stroke occurs when blood vessels in the brain rupture or become occluded. Deficits resulting from stroke are usually maximal at onset (rather than steadily worsening, like the symptoms of a brain tumor), last more than 24 hours, and coincide with injury to the brain's vasculature as demonstrated by neurological and neuroimagining examination. Typical symptoms include muscular weakness, loss of sensation, problems with vision, and impaired speech. Depending on the location and severity of neuronal damage, additional symptoms, including loss of consciousness, may occur. There are two main types of stroke: hemorrhagic and thrombotic (also known as ischemic). A hemorrhagic stroke may be caused by a ruptured cerebral blood vessel, a ruptured intracranial aneurysm, or an arterio-venous malformation leading to an intracerebral hemorrhage in or near the brain. (In this report, we do not address hemorrhage from arterial aneurysms and arterio-venous malformations, as their epidemiology differs significantly from that of other types of stroke). A thrombotic stroke results from the occlusion of one or more cerebral blood vessels. A thrombus may form directly on a diseased small vessel, or a large-vessel atherosclerotic plaque may embolize and block a smaller cerebral artery. A temporary interruption of the blood supply to a region of the brain, called a transient ischemic attack (TIA), usually results from narrowing of the carotid arteries due to plaque accumulation (carotid stenosis). Patients with TIAs experience a sudden onset of stroke symptoms and a focal loss of brain function lasting less than 24 hours. Studies from the United States and Europe indicate that within 2 to 5 years of their first TIA, between 8 and 33 percent of patients go on to have a full stroke.
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Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World SCOPE OF THE PROBLEM Mortality Stroke is a leading cause of disability and mortality throughout the world.[3,4] According to the World Health Organization (WHO), stroke kills approximately 4.6 million people (9 percent of all deaths) each year, and ranks as the second most common cause of mortality worldwide. The 1996 Global Burden of Disease study revealed that cardiac and cerebral vascular diseases have surpassed infectious and parasitic diseases to become the leading causes of death in the developing world, India and sub-Saharan Africa excepted.[ 5] In the People's Republic of China (PRC) alone, more than 1 million people die from stroke each year—three times the number of those who die from ischemic heart disease in that country. Among men and women aged 30–69, cardiac and cerebral vascular diseases cause three times as many deaths worldwide as infectious and parasitic diseases. This age group generally comprises the most economically productive members of the workforce, a situation that serves to amplify the toll of death and disability associated with stroke and related disorders.[ 2,7] In South Africa, for example, stroke accounts for between 8 and 10 percent of all reported deaths and 7.5 percent of deaths among people of prime working age, 25 to 64 years old. Table 10-1 lists several additional reports describing stroke mortality in diverse populations. While the wide range of mortality rates shown may to some extent reflect population differences in exposure to risk factors for stroke (as discussed further below), the variation probably results as well from methodological differences among studies.[ 9] For example, in sub-Saharan Africa, most data on stroke mortality have been hospital-based, although the majority of stroke deaths in that region are thought to occur at home. Box 10-1 describes an attempt to take this situation into account and produce more accurate measures of stroke mortality in urban and rural Tanzania. Some studies in developing countries have found significant geographic  and ethnic [12,13] variations in stroke mortality within the same nation.[14,15] Other researchers, however, point out that such results need to be interpreted with caution as no standards exist for classifying ethnic groups. Comparative data for more than 30 countries from 1950 to 1990 show increasing mortality from stroke in Eastern Europe, contrasting with declines seen in the United States; Europe; and Argentina, Chile, Uruguay, and Venezuela. Social and Economic Costs In addition to causing early death, stroke results in significant nonfatal illness and disability. In the 1996 Global Burden of Disease study, stroke ranked as the sixth leading cause of lost years of healthy life and was responsible for about 2.4 percent of disability-adjusted life years (DALYs) worldwide. Projections for 2020 place cerebrovascular disease—a more general term that describes any abnormality
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Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World BOX 10-1 Stroke Mortality in Urban and Rural Tanzania Measuring stroke mortality in sub-Saharan Africa presents numerous problems. General mortality rates in this region are not well known because of the lack of reliable death certification systems, and few data are available on cerebrovascular disease or its risk factors. Community-based research in developed countries indicates that many people die of a first stroke before reaching a hospital, a scenario that appears even likelier to occur in Africa. A recent study by Walker and co-workers attempted to circumvent these problems through the use of key informants and so-called verbal autopsies in three contrasting regions of Tanzania, with a total population of more than 300,000. The three surveillance areas were urban Dar-es-Salaam; Hai district, a relatively prosperous rural area; and Morogoro district, an impoverished rural area. Over a 3-year period, key informants provided mortality information for an annual or semiannual census. For each reported death, clinical officers identified the cause through the use of a standard questionnaire presented to family members of the deceased; the results were coded by physicians and further validated through a variety of measures. The study determined age-specific stroke mortality rates for men and women in the three areas, compared with 1993 rates for England and Wales. Stroke mortality rates for each of the Tanzanian communities were higher than rates in England and Wales for all age bands up to 65 years. The total number of adults dying from stroke in Tanzania is low in comparison with similar figures from other developing countries, however, since only about 6 percent of the Tanzanian population is older than 65. it appears likely that as increasing numbers of people in sub-Saharan Africa survive to old age, there will be a significant increase in mortality due to stroke. Source: 
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Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World TABLE 10-1 Stroke Mortality: Selected Studies Country Population Method Rates (per 100,000) China (PRC)  Urban and rural (29 provinces, 5,800,000) Door-to-door survey with follow-up neurological examination 77 (crude) 81 (age-adjusted) China (PRC)  Rural (Inner Mongolia) Door-to-door survey with follow-up neurological examination 45 (age-standardized) China (PRC)  Rural (Tibet) Door-to-door survey with follow-up neurological examination 370 (age-standardized) Mexico  Urban and rural; multiple sites in Mexico Population-based; epid emiological surveillance data from hospital records and surveys 25 (crude) Philippines  Urban and rural Vital statistics records from ministry of health, 1963-76 32 Singapore  Urban and rural Population-based; annual death registries, 1970–1994 50–60 (crude) 59 (age-standardized) South Africa  Rural; 35 years and older (932 deaths) Community-based study; census, death records, and verbal auto psies 127 (over 35 years) 80 (35 to 64 years) 338 (over 64 years) Tanzania  Three regions (urban poor and prosperous rural); 307,820 popul ation (181,888 aged 15 or older) Death and hospital records confirmed with verbal autopsies 95–420 for men, 55–317 for women (age-adjusted; 15 years and older); 35–65 for men, 27–88 for women (age-adjusted; 15–64 years) Venezuela  All ages Ministry of health records 30 Vietnam  Three regions (Ho Chi Minh City and two rural areas) with a total population of 52, 649 Door-to-Door survey with follow up examination 131 (age-adjusted)
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Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World of the brain resulting from blood vessel pathologies—fifth among the causes of disease burden as measured in DALYs for developing countries, and fourth worldwide. The extensive and intensive care frequently required by stroke victims places disproportionate demands on limited resources for health care in many developing countries. For example, in one Zambian bush hospital during a 6-month period, stroke patients comprised less than 5 percent of total admissions but consumed 14 percent of all intensive care unit bed days. When a person dies or becomes disabled as a result of stroke, the negative repercussions of that event extend beyond the victim's family to the community, the nation, and the global economy. The death of an adult family member can have a devastating impact on the household. Caring for a family member disabled by stroke can harm the caregiver 's own health, productivity, and ability to earn money. The resulting losses in production, earnings, investment, and consumption affect local, regional, national, and global economies. Among many developed-country populations, 0.2 percent suffer a stroke each year. Of those afflicted, one-third remain permanently disabled, and one-third make a reasonable recovery. The two-thirds who do not die form a large pool (about 1 percent of the population) of stroke survivors, of whom at least half are disabled, making stroke the most important single cause of severe disability among people living in their homes.[ 29] Unfortunately, such studies have not attempted to assess or document the social and economic costs of stroke in developing countries, where more than two-thirds of all strokes are thought to occur.[ 9] The social and economic costs of stroke in developing countries are expected to persist—and probably increase—over the next two decades. The following factors are most frequently cited to explain this trend : Reductions in infant and childhood mortality, allowing greater proportions of people in developing countries to survive beyond age 64, when 75 percent of all strokes occur.[2,9,30] The growing adoption of behaviors and lifestyles known to elevate stroke risk, such as tobacco use and high saturated fat intake, that can lead to hypertension, obesity, and diabetes (see the discussion of risk factors below). For example, current predictions indicate that by 2020, 12 percent of all deaths and 9 percent of all DALYs will be attributable to tobacco alone; the vast majority of this increased burden is projected to arise in developing countries.[ 32,33] Although evidence from industrialized countries demonstrates that stroke and other vascular disorders can be significantly reduced through interventions at the individual, community, and national levels, this knowledge and experience have yet to be applied systematically among the populations of developing countries.[34,35] There is a lack of awareness of cost-effective options for reducing the impact of stroke, as well as concern in some quarters that such investments may
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Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World detract from efforts to control communicable diseases and to promote maternal, child, and reproductive health. Along with the above factors, which influenced the rise of stroke and other cardiovascular and cerebrovascular diseases in developed countries and are now becoming prominent in the developing world, there appear to be additional factors specific to developing populations that could exacerbate the pending epidemic of these diseases. For example, researchers have documented relatively high rates of obesity, hypertension, glucose intolerance, and ischemic heart disease—all risk factors for stroke—among adults whose growth was stunted during childhood. Among populations where food has been historically scarce, “thrifty genes” appear to predispose bearers to obesity and diabetes when food is plentiful. The seriousness of the threat posed by cerebro- and cardiovascular disease must be clearly demonstrated to the governments of developing countries. Stroke deserves particular attention as a preventable and treatable illness with profound medical, economic, and social consequences. Confronting the epidemic of stroke that threatens developing countries will require a better understanding of the origins of the disease, prediction of its magnitude, and timely implementation of preventive and case-management strategies. PREVALENCE AND INCIDENCE Prevalence and incidence rates for stroke vary dramatically from one population to another. The reasons for this heterogeneity are not completely understood and are currently being explored in several large-scale epidemiological studies. Three broad sets of factors have been proposed as likely explanations for differences in the prevalence and incidence of stroke : The stage of economic development, which appears to play a role not only in the prevalence and incidence figures for a given geographic region, but also in the specific type of stroke present. Differences in behavior and lifestyle that expose populations to varying types and degrees of risk factors, such as smoking, physical inactivity, obesity, ethanol use and abuse, and high sodium and saturated fat intake. Differences in hereditary predisposition to cerebral and cardiovascular diseases. Although the results of research to determine specific genetic risk factors for stroke have been inconclusive, epidemiological data suggest the existence of significant differences in the cause, type, and prevalence of stroke among different ethnic populations.[ 36] Genetic studies in diverse populations could provide a new perspective on the basic pathogenic mechanisms underlying the vascular disease process. Developing countries have recently begun to join the developed world in experiencing the so-called epidemiological transition of diseases. Control of infectious and parasitic diseases, along with improvements in nutrition, have
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Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World lengthened the average life span in many parts of the world. As a result, the spectrum of disease is shifting away from communicable diseases and perinatal and nutritional disorders to predominantly noncommunicable diseases, most notably cardiovascular disease.[37,38] Early in the epidemiological transition, most strokes tend to be hemorrhagic. Hypertension is an important risk factor for this type of stroke, which often occurs in people with low blood cholesterol levels. As the transition progresses, thrombotic strokes account for an increasing fraction of mortality, and ultimately become the most prevalent stroke type. During the 1980s, WHO undertook a major international effort to monitor stroke prevalence and incidence in 10 countries of Asia and Europe: the Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) Project.[3,39] Unfortunately, neither Latin American nor African countries were studied. Despite this limitation, the MONICA Project, through the use of uniform and statistically valid procedures, provided comparisons across populations in areas as different as Novosibirsk in the Russian Federation and Fruili in Italy. In the ideal, community-based settings in which MONICA was conducted, over-all stroke occurrence and mortality rates were found to be twice as high among men than women, and higher in Finland, Lithuania, the Russian Federation, and the PRC than in western and central Europe. MONICA populations were defined as all residents of the study areas according to geographic and administrative boundaries. Stroke events were identified through standard protocols, and cases were coded according to the International Classification of Diseases (ICD). Death certificates provided the major source of data on stroke mortality; hospitalized cases were identified from admission lists, discharge diagnoses, and other available medical record information. While considerable effort was made to ensure the quality of the data, researchers have noted some discrepancies, as well as a general need to interpret multinational comparisons of stroke statistics with caution. Prevalence Table 10-2 shows the broad range of stroke prevalence reported in studies conducted throughout the developing and developed worlds. Similar variation in stroke prevalence has also been reported within single countries. In India, for example, neuroepidemiological data on stroke collected over the past 30 years have revealed prevalence rates as low as 44 in rural areas and as high as 842 per 100,000, among the urban Parsi community in Bombay. Studies conducted across many regions of India indicate that stroke accounts for 2 percent of hospital registrations, 1.5 percent of medical registrations, and 9 to 30 percent of neurological admissions.[ 41,42,43 and 44] Reliable studies of stroke prevalence would be particularly valuable in estimating the impact of the disease since, as noted above, many stroke patients survive with some disability for many years. However, most studies on stroke prevalence in developing countries have been based on hospital records, and thus describe only those patients —a minorityin many low-income communi-
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Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World ties—who received hospital treament. Community-based research, while difficult to perform in developing countries, represents the best means of obtaining accurate estimates of stroke prevalence—information that could be used not only for health care planning, but also for clues to risk factors, preventive strategies, and treatments.[22,45] Two examples of the few existing studies of this type were conducted in the Hai district of Northern Tanzania  and the island of Kinmen in the Republic of China (Taiwan). Although the focus of each study was quite different, both employed door-to-door surveys, followed by neurological examination to confirm diagnoses. Incidence As is the case with studies of stroke mortality and prevalence, reports of stroke incidence rates indicate wide variation throughout the developing world (see Table 10-3). Rates of 200 per 100,000 or higher have been reported in several Asian countries [6,24,26] and in Russia, while stroke appears to be nonexistant in Kitava, New Guinea. Researchers have offered a variety of explanations for low stroke incidence, including young populations, lack of influence of Western diets, low diastolic blood pressure, and low cholesterol levels.[ 49,50] A substantial decrease in stroke mortality noted over recent years in the United States remains unexplained, but appears to be due to individual lifestyle modifications, as well as improvements in the general environment and in medical care. Several studies have revealed high rates of stroke incidence among young people in low-income countries as compared with the developed world. In India, for example, an analysis of the Stroke Registry established at NIMHANS showed that 20 percent of strokes occurred in people younger than age 40. Stroke among children, while comparatively rare relative to adults, may prove more common among developing populations prone to sickle cell anemia, an apparent risk factor for stroke,[ 52] as well as other conditions discussed below. Incidence studies have also revealed variation in the occurrence of the two types of stroke among different populations in the developing world. In several West African countries, approximately two-thirds of all stroke cases are ischemic, and one-third are hemorrhagic.[ 53,54,55 and 56] In Iran, two-thirds of strokes were found to be ischemic in origin.[ 57] In the PRC, hemorrhagic stroke is as common as ischemic. Consistently, 30 percent of stroke cases are hemorrhagic in Singapore, Malaysia, Thailand, Indonesia, Hong Kong, the Philippines, Taiwan, and South Korea.[58,59] Comparing stroke incidence in different countries and observing incidence trends in specific populations may increase our understanding of the disease. However, such comparisons cannot be made until studies of stroke incidence use the same definitions, methods, and mode of data presentation. While MONICA and other recent studies have begun to address this problem in some parts of the world, the profound lack of comparable incidence data for Africa, Asia, and South America largely excludes the developing world from such analyses.[60,61]
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Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World TABLE 10-2 Stroke Prevelance: Selected Studies Country Population Method Rate (per 100,000) China (PRC)  Urban and rural sites (5,800,000) Door-to-door survey with follow-up neurological examination 260 (age-adjusted) 246 (crude) Colombia  Urban (13,588) Door-to-door survey 559 Ecuador  Rural (1,113) Door-to-door survey; questionnaire; neurological screening examina tion 360 Ethiopia  Rural (60,820) Door-to-door survey 15 (disability due to stroke only) India  Urban; Parsis living in Bombay (14,010) Detailed neuroepidemiological study 842 India  Rural; Kashmir House-to-house census 143 Nigeria  Rural (18,594) Questionnaire; examination 58 Peru  Rural (3,246) Door-to-door survey 647 Saudi Arabia  Hospital-based (500) Review of records; diagn osis confirmed by computed tomography 186 Taiwan (ROC)  3,915 residents of the islet of Kinmen, age 50 and over Door-to door interview; neurological examination of all partici pants 2,450 (lifetime prevalence Tanzania  Rural; Hai District 148,135 (82,152 age 15 and over) House-to-house census, interview, examina tion 73 (127 age 15 and over) Tunisia  Urban (34,874) Community-based survey; follow-up control survey 140 Vietnam  Three regions (Ho Chi Minh City and two rural areas) with a total population of 52, 649 Door-to-door survey with follow-up neurological examination 608 (age-adjusted)
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Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World TABLE 10-3 Stroke Incidence: Selected Studies Country Population Method Rate (per 100,000) China (PRC)  5,800,000 Door-to-door survey with follow-up neurological examination 116 (standardized to world populations) 110 (crude) Singapore  Urban and rural (5,920) Cohort study examining three previous cross-sectional surveys and longitudinal follow-up from national registry data Chinese: 230 (male); 120 (female) Malay: 160 (male); 280 (female) Indian: 220 (male); 150 (female) Iran  44 (men) 59 (women) Kuwait  Urban Hospital and primary care clinic registries with clinical evaluation 28 (crude) 145 (age-adjusted) Libya  Benghazi (52,000) 63 Nigeria  Urban (Ibadan) Hospital-based; stroke registry 74.8 (standardized to world population) Papua New Guinea  Kitava Island; traditional horticulturalists uninfluenced by Western diets (220) Cardiovascular and neurological screening examinations 0 Russia  Novosibirsk (150,000) Population-based; stroke registry 232 Saudi Arabia  545,000 Stroke registry (1989–93) 30 (crude); 126 (standardized to 1976 U.S. population) Taiwan (ROC)  3,915 residents of the islet of Kinmen, age 50 and over Door-to door interview; neurological examination of all partici pants 527 Tunisia  Tunis Stroke registry 192 (age-adjusted, 45 years and older) Vietnam  Three regions (Ho Chi Minh City and two rural areas) with a total population of 52,649 Door-to-door survey with follow-up neurological examination 250 (age-adjusted) Zimbabwe  Urban (black residents of Harare; total population 887,768) Prospective community-based 68 (standardized to world population); 30.7 (crude)
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Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World Recommendation 10-1. Data collection should be improved to provide accurate information about stroke mortality, morbidity, incidence, prevalence, and mechanisms in developing countries using culturally sensitive tools and diagnostic techniques. Pathological studies of stroke should be conducted to determine the relative prevalence of various stroke subtypes among several diverse representative populations in developing countries. This research would be greatly enhanced if conducted in collaboration with research centers in high-income countries utilizing other existing data and research mechanisms. RISK FACTORS The term “risk factor” was coined by investigators in the Framingham Heart Study, one of the largest, longest-running, and best-known epidemiological studies of its kind. Considerable data on risk factors for stroke have come from the 850 participants who have experienced a stroke since the U.S. study began in 1950. While several of the predominant modifiable risk factors for stroke identified in the Framingham study—most notably hypertension, diabetes, and smoking—appear generalizable to many populations, data documenting the relative impact of these factors in developing countries are sparse. This represents fertile ground for future epidemiological studies, as does the possibility that new stroke risk factors of particular significance in developing countries might be identified (for example, infectious agents, nutritional factors, or developmental syndromes that rarely occur in developed countries). At present, the risk factors described in this section represent the most promising targets for preventing and treating stroke in the developing world. Additional factors associated with stroke outcome are subsequently discussed. Physiological Hypertension The foremost risk factor for stroke throughout the industrialized world, hypertension may play an even greater role in causing stroke in low-income communities. Epidemiological studies among populations of East Asia, including the PRC  and Africa [80,81], indicate that controlling elevated blood pressure in these populations could prevent proportionately more strokes than equivalent measures in Western populations. The reasons for the apparently stronger influence of hypertension on strokes among East Asian and black African populations remain to be identified, but may include both genetic and environmental effects, as well as longer exposure to untreated conditions of hypertension. Both populations were found to suffer a far higher proportion of hemorrhagic strokes as compared with Western populations.
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Representative terms from entire chapter: