Part II

INTRODUCTION

In addition to reviewing the overall burden of disease attributable to brain disorders and formulating a strategic framework to reduce that burden in developing countries, presented in Part I of this report, the committee was also charged to address specifically the following group of representative disorders: developmental disabilities, epilepsy, bipolar disorder, schizophrenia, unipolar depression, and stroke. The committee reviewed evidence of the impact of each of these disorders in developing countries and identified strategies to reduce that impact through prevention and low-cost treatment, research and development, and capacity building. The results of this process are presented in the next six chapters, which comprise Part II of this report.

Several factors were considered in selecting these particular disorders for study. First, each ranks among the most prevalent of neurological, psychiatric, or developmental disorders worldwide and is known to cause significant disability. Second, these disorders represent a spectrum of disease affecting people at every stage of life, from fetal development through old age; their order of presentation in the following chapters, which begins with developmental disabilities and concludes with stroke, reflects this chronological progression. Finally, these particular classes of disorder appeared to be strong candidates for cost-effective interventions, and therefore critical targets for reducing the overall burden of disease associated with brain disorders. It is hoped that future studies on other brain disorders of public health significance, such as Alzheimer's disease, injuries to the central nervous system, substance abuse, and posttraumatic stress disorder, will build on this initial effort.



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Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World Part II INTRODUCTION In addition to reviewing the overall burden of disease attributable to brain disorders and formulating a strategic framework to reduce that burden in developing countries, presented in Part I of this report, the committee was also charged to address specifically the following group of representative disorders: developmental disabilities, epilepsy, bipolar disorder, schizophrenia, unipolar depression, and stroke. The committee reviewed evidence of the impact of each of these disorders in developing countries and identified strategies to reduce that impact through prevention and low-cost treatment, research and development, and capacity building. The results of this process are presented in the next six chapters, which comprise Part II of this report. Several factors were considered in selecting these particular disorders for study. First, each ranks among the most prevalent of neurological, psychiatric, or developmental disorders worldwide and is known to cause significant disability. Second, these disorders represent a spectrum of disease affecting people at every stage of life, from fetal development through old age; their order of presentation in the following chapters, which begins with developmental disabilities and concludes with stroke, reflects this chronological progression. Finally, these particular classes of disorder appeared to be strong candidates for cost-effective interventions, and therefore critical targets for reducing the overall burden of disease associated with brain disorders. It is hoped that future studies on other brain disorders of public health significance, such as Alzheimer's disease, injuries to the central nervous system, substance abuse, and posttraumatic stress disorder, will build on this initial effort.

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Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World The framework for studying each of the selected disorders or groups of disorders included an overview of the available epidemiological parameters, a review of the existing knowledge base to support intervention, and projections of the feasibility, cost, and expected impact of proposed interventions. Wherever possible, the committee based its review and recommendations on evidence from a broad range of settings in the developing world; unfortunately, due to the limited available research on most brain disorders in developing countries, they were frequently forced to make qualified extrapolations based on data from the developed world. In most cases, direct correlations appear to exist between developed and developing countries. For example, many proven risk factors for stroke have been established in developed countries (such as hypertension, high-fat and sodium diets, and diabetes), and these risk factors are of growing concern in developing countries. Though extensive data do not exist on prevention methods for controlling or eliminating these risk factors in developing countries, it can be said that such efforts would bear similar reduction in stroke mortality as has been observed in developed countries. In the few instances where correlations might be skewed by differences between developed and developing countries, these limitations are clearly noted. As one might expect, several observations regarding the impact and outlook for reducing the burden of specific disorders presented in the chapters of Part II mirror comments in Part I that pertain to many or all brain disorders. These points are reiterated in order to build the most complete picture possible of each individual disorder. However, since the discussions of specific brain disorders presented in Part II are ultimately intended to be viewed in the context of the general discussion and strategies that appear in Part I, readers are advised to familiarize themselves with the introductory chapters of this report before proceeding to the chapters in Part II.

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Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World Summary of Findings: Developmental Disabilities in Developing Countries Developmental disabilities impose enormous personal, social, and economic costs due to their early age of onset and frequent result of lifetime dependency. The magnitude of the impact of developmental disabilities is largely unknown and unrecognized in low-income countries today, where more than 80 percent of the world's children are born. The prevalence of many of the specific causes of developmental disabilities (including genetic, nutritional, infectious, and traumatic causes) appears to be elevated in low-income countries. Numerous prevalent diseases and common environmental factors have been found to contribute to or increase the risks for developmental disabilities. Many of these causes—including nutritional deficiencies, infection, environmental toxins, and perinatal complications—are preventable, either by controlling the underlying condition, or by treating illness or injury to prevent progression to long-term disability. Rehabilitation for developmental disorders is likely to be cost-effective given the benefits of reduced dependency and improved productivity and quality of life. Models of low-cost rehabilitation include community-based rehabilitation, school-based models, institution- and hospital-based models, and various primary health care models and national strategies, all of which can be integrated into low-cost comprehensive treatment programs.

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Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World 5 Developmental Disabilities DEFINITION Developmental disabilities include limitations in function resulting from disorders of the developing nervous system. These limitations manifest during infancy or childhood as delays in reaching developmental milestones or as lack of function in one or multiple domains, including cognition, motor performance, vision, hearing and speech, and behavior. Table 5-1 provides a listing of the major categories of developmental disability with corresponding International Classification of Diseases (ICD)-10 codes.[1] To varying degrees, the causes of many other neurological and psychiatric disorders not typically designated as developmental disabilities may also be traced to early neurodevelopment. For several of the disorders discussed in subsequent chapters—specifically epilepsy, depression, and schizophrenia—evidence indicates such a causal relationship.[ 2,3,4,5,6,7,8,9,10 and 11] The clinical features of developmental disabilities are variable in severity as well as in the specific areas of function that are limited. Brief descriptions of the clinical features of each of the broad categories of developmental disability are provided below. It may be noted that children with developmental disabilities are often affected in multiple domains of function because of the nature and extent of brain impairment or increased susceptibility to other causes of disability (e.g., malnutrition, trauma, infection) among children with a single disability.

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Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World TABLE 5-1 Major Categories of Developmental Disability with Corresponding ICD-10 Diagnostic Codes (when available)   ICD-10 Code Cognitive   Mental Retardation   Mild (IQ approximately 50–69) F70 Moderate (IQ approximately 35–49) F71 Severe (IQ approximately 20–34) F72 Profound (IQ below 20) F73 Specific Learning Disabilities F81 Reading (Dyslexia) F81.0 Mathematics (Dyscalculia) F81.2 Other   Motor   Cerebral Palsy G80 Post-Polio Paralysis B91 Muscular Dystrophies G71.0 Spina Bifida Q05 Spinal Muscular Atrophies G12 Other M01–M03.   Q65–Q79 Vision   Refraction Disorders H52 Cataract infantile and juvenile H26.0 Chorioretinal Inflammation, infectious or parasitic H32.0 Nightblindness, due to vitamin A deficiency E50.5 Other Q10–Q15 Hearing   Conductive and Sensorineural H90 Other Q16 Hearing and Speech   Specific Speech Articulation Disorder F80.0 Expressive Language Disorder F80.1 Receptive Language Disorder F80.2 Behavior   Attention-Deficit Hyperactivity Disorder F90.0 Pervasive Developmental Disorder, including autism F84 Other F80–F98 Source: [1] Cognitive Disabilities Cognitive disabilities in children include mental retardation as well as specific learning disabilities in children of normal intelligence. Mental retardation is defined as subnormal intelligence (intelligence quotient [IQ] more than two standard deviations below that of the population mean), accompanied by deficits in adaptive behavior. Grades of mental retardation are typically defined in terms

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Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World of IQ. Children with mild mental retardation, the most common form, are limited in academic performance and consequently have somewhat limited vocational opportunities. Adults with mild mental retardation typically lead independent lives. Children with more severe grades of mental retardation (moderate, severe, and profound) are more likely to have multiple disabilities (e.g., vision, hearing, motor, and/or seizure in addition to cognitive disability) and to be dependent on others for basic needs throughout their lives. In contrast, specific learning disabilities result not from global intellectual deficit, but from impairments in one or more of the specific “processes of speech, language, reading, spelling, writing or arithmetic resulting from possible cerebral dysfunction.”[12] Children with specific learning disabilities are usually identified as such only after entering school, where a significant discrepancy is noted between their achievements in specific domains and their overall abilities. With special educational accommodations, these children may learn to overcome their limitations and demonstrate normal or even superior levels of achievement. Motor Disabilities Motor disabilities include limitations in walking and in use of the upper extremities (arms and/or hands). Some motor disabilities also affect speech and swallowing. Severity can range from mild to profound. Motor disabilities diagnosed in infancy or childhood include cerebral palsy, which results from damage to motor tracts of the developing brain; paralysis following conditions such as poliomyelitis and spinal cord injuries; congenital and acquired limb abnormalities; and progressive disorders, such as the muscular dystrophies and spinal muscular atrophies. Cerebral palsy results from a permanent, nonprogressive damage or insult to the developing brain. Affected children therefore may manifest a variety of motor dysfunctions, depending on the specific location of the damage. Involvement of the motor cortex produces spasticity, while involvement of the cerebellum results in hypotonia with or without ataxia. Involvement of the basal ganglia leads to dyskinesia and dystonia. Individuals with cerebral palsy often have other disabilities as a result of concomitant insults to various areas of the brain. Such disabilities include mental retardation, learning disabilities, epilepsy, language disorders, and behavioral problems. Similarly, some of the progressive motor disorders, such as muscular dystrophy, can be accompanied by cognitive disabilities. In contrast, in many forms of paralysis, such as that due to poliomyelitis or spinal cord injury, and congenital or acquired limb abnormalities, the disability is more likely to be restricted to motor skills or mobility. Vision, Hearing and Speech Disabilities The prevalence of low vision, blindness, and hearing loss increases with age, making these disabilities conditions that affect primarily adults. A number of important causes of vision as well as hearing disability have their onset early

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Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World in life, however, and may be considered neurodevelopmental (as discussed further below). Refractive errors, the most common form of vision impairment, are especially problematic for children in low-income countries because eyeglasses and basic vision care services are unavailable to many. However, refractive errors are readily amenable to low-cost methods of diagnosis and intervention, which can become a component of primary care screening services.[13,14,15,16,17 and 18] Learning to speak depends on the ability to hear and repeat sounds. The optimal period for speech acquisition is the first 2 years of life; a child who does not speak by the age of 5–6 will have difficulty developing intelligible speech thereafter. It is therefore important to screen young children for hearing impairment and to evaluate the hearing of a child who is suspected of having mental retardation or delay in speech development. Behavioral Disorders In most of the developing world, resources for mental health care are far more limited than those for physical care. Therefore, the majority of children with psychological or behavioral disorders go undiagnosed or untreated. Although formal data are lacking, it is probable that behavioral problems are more common in low-income than in wealthier countries because of the excess prevalence of poverty, war, famine, and natural disasters in the developing world.[19,20] Moreover, recent social transformations and rapid urbanization in many low-income countries have produced adverse effects, such as residential displacement and disruption of traditional family systems, that have in turn resulted in large numbers of homeless and displaced children. Behavioral disorders not necessarily linked to psychosocial precursors include autism and attention-deficit and hyperactivity disorders. These disorders can have profound effects on academic achievement and on families. Current research is seeking to identify structural and functional correlates in the brain for a range of behavioral disorders. SCOPE OF THE PROBLEM Developmental disabilities impose enormous personal, social, and economic costs because of their early onset and the lifetime of dependence that often ensues. Children with disabilities often have limited educational opportunities, and as they grow older, limited employment options, productivity, and quality of life. Yet the costs of developmental disabilities are difficult to quantify in settings where relevant data and services are lacking. As a result, in low-income countries today, where more than 80 percent of the world's children are born, the magnitude of the impacts of developmental disabilities on individuals, families, societies, and economic development remains largely unrecognized and has yet to be addressed from a policy perspective.

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Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World While disability-adjusted life years (DALYs; for definition see Chapter 2) have been computed for some of the specific causes of developmental disability, such as meningitis and iodine deficiency,1 these figures do not convey the full proportion of cases within a given category of disorder that result in early and lifelong disability or death. Nor are DALY estimates currently available for the broad categories of developmental disability listed in Table 5-1 or for developmental disability as a whole. What is needed before useful DALY or other measures of impact can be calculated for developmental disabilities is accurate and up-to-date information from low-income countries on the prevalence and impacts of long-term functional limitations originating early in life as a result of both known and unknown causes. These data would allow an assessment of the costs and impacts of developmental disabilities against the costs of their prevention, which would in turn facilitate rational decision making and resource allocation with respect to child health and development. Without this information, there is a tendency to conclude that in low-income countries, more pressing issues preclude the allocation of resources for the prevention of developmental disabilities. While the focus of this report is on the public health dimensions of developmental disabilities in children, including etiology, quantitative indicators, and strategies for prevention, we cannot neglect the fact that the major impacts of developmental disabilities in all countries are borne by families and individuals as a result of experiences that are difficult to quantify. These experiences include stigma, lost hopes and opportunities, discrimination, increased stress and daily challenges brought on by lifelong impairment, handicap, and social isolation. It is hoped that as countries and governments begin to take responsibility for the public health dimensions of developmental disabilities, improved awareness and management of the human dimensions of these disorders will follow. As societies and economies become increasingly information-oriented and dependent on highly skilled and literate workers, it is critical that children everywhere have an opportunity to attain their optimal levels of cognitive and neurological development. The persistence of excess prevalence rates of developmental disabilities observed in low-income countries today is both a consequence of poverty and poor resource allocation and an impediment to future social and economic development. 1   The most recent DALY figures in low- and middle-income countries for risk factors discussed in this chapter include HIV/AIDS, 5.5 percent; polio, 0.0 percent; measles, 2.4 percent; tetanus, 1.0 percent; meningitis, 0.4 percent; malaria, 3.1 percent; Japanese encephalitis, 0 percent; trachoma, 0.1 percent; protein-energy malnutrition, 1.2 percent; iodine deficiency, 0.1 percent; vitamin A deficiency; 0.2 percent; anemias, 1.9 percent; road traffic accidents, 2.7 percent; homicide and violence, 1.6 percent; war, 1.7 percent.

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Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World PREVALENCE AND INCIDENCE Valid generalizations about the frequency and causes of developmental disabilities are difficult to make for any population because of the lack of true incidence data. Data on incidence (i.e., the frequency of newly occurring cases) are preferable to those on prevalence (i.e., the number of existing cases in a population) for investigating etiology because they allow causes to be distinguished from factors associated with survival. For developmental disabilities, incidence data are not available because only a minority of cases survive long enough to be identified, while for those who do survive, the onset of recognizable disability is often insidious as development unfolds.[21] In relatively wealthy countries, epidemiological studies of developmental disabilities are generally cross-sectional and use service records or registries to ascertain prevalent cases. Thus, in contrast to incidence, a great deal is known about the prevalence of developmental disabilities in populations where affected children receive services. In populations lacking universal schooling and formal services for children with disabilities, the relatively few prevalence studies conducted to date have employed door-to-door surveys designed to identify all children with developmental disabilities in defined populations. The validity and interstudy comparability of prevalence estimates from these surveys depend on the quality and comparability of the assessment methods and diagnostic criteria used, which can be difficult to appraise from published reports. In addition, even when valid methods have been employed, there may be questions about the cross-cultural appropriateness of standardized tests of intelligence and behavior used to diagnose disabilities in children of diverse cultural and socioeconomic backgrounds.[22] An additional problem in comparing prevalence studies from developing countries is that elevated infant and child mortality rates may curtail the prevalence of developmental disabilities in the population. If improvements in child survival are made without concomitant reductions in the occurrence of new cases of developmental disabilities, the result will be an increase in the population prevalence of disability due to the increased longevity of children with disabilities.[23,24 and 25] A review of the prevalence studies of developmental disabilities published between 1970 and 1999 shows that most of the available data are restricted to the relatively high-income populations of developed countries in Europe, North America, and eastern Asia. Yet during this period, more than 80 percent of the world's children resided in low- and middle-income countries. This imbalanced knowledge is both a cause and a consequence of the fact that the public health impact of childhood disabilities has received little attention in low-income countries. Available evidence, however, suggests that many of the causes of disability in children are more prevalent in developing than in developed countries.

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Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World Prevalence of Cognitive Disabilities Prevalence data on an aggregate of cognitive disabilities in developing countries are not available. Figure 5-1 summarizes the range of prevalence estimates for severe mental retardation among children in populations throughout the world. The studies are listed in descending order by per capita income of the countries in which they were conducted. These estimates show a clear tendency toward elevated prevalence in low-income countries. In developed countries, the prevalence of severe cognitive disability is consistently found to be in the range of 3 to 5 per 1,000 children. By contrast, the prevalence of severe cognitive disability in developing countries ranges from a low of 2.9 per 1,000 children in Beijing to a high of 22 per 1,000 in slum areas surrounding Lahore, Pakistan. The majority of estimates from low-income countries are above 5 per 1,000, while no estimates from developed countries are this high.

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Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World Summary of Findings: Epilepsy in Developing Countries Eighty percent of the more than 40 million people with epilepsy live in developing countries, where cultural factors frequently exacerbate the burden of disease on patients and their families. Even when assistance is sought, a treatment gap as high as 90 percent still affects some rural populations in low-income countries. Many risk factors for epilepsy have been identified, including birth trauma, parasitic infections (most notably cysticercosis), bacterial and viral infections, head injuries, febrile seizures, and genetic factors. Local variation in risk factors at least partly explains the marked heterogeneity in the prevalence and incidence of the disease throughout the world. Key preventive measures likely to significantly reduce the incidence of epilepsy include prenatal care, avoidance of labor and delivery complications, safety measures against head injuries, control of infectious and parasitic diseases, and genetic counseling for potential marriage partners who have the disease. Phenobarbital is recommended for the treatment of partial and generalized tonic-clonic epilepsies in developing countries due to its efficacy for a wide range of seizure types, its low cost, and its superiority to both phenytoin and carbamazepine in recent community-level studies. The lack of adequate drug production facilities and high prices for imported drugs restrict the availablity of anti-epileptic drugs in developing countries.