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Suggested Citation:"6 Epilepsy." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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6

Epilepsy

DEFINITION

In recent epidemiological studies, epilepsy is defined by the recurrent presentation of two or more unprovoked seizures. This definition excludes single afebrile episodes, febrile seizures, and seizures that are manifestations of altered metabolic states, alcohol or drug withdrawal, and other transient cerebral insults.[1,2,3,4,5,6,7,8,9,10 and 11]

The diagnosis of epilepsy thus defined is basically clinical, because no single laboratory test can confirm the absence of the condition. The test most commonly employed for the diagnosis of epileptic abnormalities is the electroencephalogram (EEG). While the EEG is a useful tool that can assist the clinician in arriving at a diagnosis of epilepsy, however, it is not always a sensitive or specific test.[3,4]

Epilepsy manifests with several types of seizures, differing in age of onset, response to treatment, prognosis, electroencephalographic correlates, and risk factors.[12] Moreover, epilepsy that is secondary to a parasitic infestation of the brain is a disorder altogether different from genetically determined epilepsies. Nonetheless, having a single term that encompasses all of these conditions makes it possible to calculate the burden of disease from both an economic and social perspective, to estimate the demand for health services planning, and to meet other public health objectives.[13] The diagnostic classification standard currently in place for epilepsy was established by the International League Against Epilepsy in 1989 (see Box 6-1).

Suggested Citation:"6 Epilepsy." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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BOX 6-1 International Classification of Epilepsies and Epileptic Syndromes

  1. Localization-related (focal, local, partial) epilepsies and syndromes.

1.1 Idiopathic (with age-related onset)

At present, the following syndromes are established, but more may be identified in the future:

  • Benign childhood epilepsy with centro-temporal spike;

  • Childhood epilepsy with occipital paroxysms; and

  • Primary reading epilepsy.

1.2 Symptomatic: This category comprises syndromes of individual variability, based mainly on anatomical localization, clinical features, seizure types, and etiological factors (if known).

1.2.1 Epilepsy is characterized by simple partial seizures with the characteristics of seizures:

  • Arising from frontal lobes;

  • Arising from parietal lobes;

  • Arising from temporal lobes;

  • Arising from occipital lobes;

  • Arising from multiple lobes; and

  • Locus of onset unknown.

1.2.2 Characterized by complex partial seizures, that is, attacks with alteration of consciousness, often with automatisms; characterized by seizures:

  • Arising from frontal lobes;

  • Arising from parietal lobes;

  • Arising from temporal lobes;

  • Arising from occipital lobes;

  • Arising from multiple lobes; and

  • Locus of onset unknown.

1.2.3 Characterized by secondarily generalized seizures with seizures:

  • Arising from frontal lobes;

  • Arising from parietal lobes;

  • Arising from temporal lobes;

  • Arising from occipital lobes;

  • Arising from multiple lobes; and

  • Locus of onset unknown.

1.3 Unknown as to whether the syndrome is idiopathic or symptomatic.

  1. Generalized epilepsies and syndromes

2.1 Idiopathic (with age-related onset—listed in order of age)

  • Benign neonatal familial convulsions;

  • Benign neonatal convulsions;

  • Benign myoclonic epilepsy in infancy;

  • Childhood absence epilepsy (pyknolepsy);

  • Juvenile absence epilepsy;

  • Juvenile myoclonic epilepsy (impulsive petit mal); and

  • Epilepsy with GTCS on awakening.

Other generalized idiopathic epilepsies, if they do not belong to one of the above syndromes, can still be classified as generalized idiopathic epilepsies.

Suggested Citation:"6 Epilepsy." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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2.2 Cryptogenic or symptomatic (in order of age)

  • West syndrome (infantile spasms, Blitz-Nick-Salaam Krampfe);

  • Lennox Gastaut syndrome;

  • Epilepsy with myoclonic-astatic seizures; and

  • Epilepsy with myoclonic absences.

2.3 Symptomatic

2.3.1 Nonspecific etiology

  • Early myoclonic encephalopathy

2.3.2 Specific syndromes

  • Epileptic seizures may complicate many disease states.

Under this heading are included those diseases in which seizures are a presenting or predominant feature.

  1. Epilepsies and syndromes undetermined as to whether focal or generalized

3.1 With bold generalized and focal seizures

  • Neonatal seizures;

  • Severe myoclonic epilepsy in infancy;

  • Epilepsy with continuous spike waves during slow-wave sleep: and

  • Acquired epileptic aphasia (Landau-Kleffner syndrome).

3.2 Without unequivocal generalized or focal features

All cases with GTCS where clinical and EEG findings do not permit classification as clearly generalized or localization-related, such as in many cases of GTCS during sleep.

  1. Special syndromes

4.1 Situation-related seizures (Gelegenheitsanfalle)

  • Febrile convulsions;

  • Isolated seizures or isolated status epilepticus;

  • Seizures occurring only when there is an acute metabolic or toxic event due to, for example, alcohol, drugs, eclampsia, nonketotic hyperglycemia, or uremia.

Source: [14]

SCOPE OF THE PROBLEM

Among brain disorders, epilepsy stands out not only because of its high prevalence and incidence rates, but in particular because of the myths and beliefs attached to the condition in various cultures and the resulting impacts on the individual, the family, and the community.[15,16,17,18 and 19] More than 40 million people worldwide have been estimated to suffer from epilepsy, and an estimated 80 percent of those individuals live in developing countries.[5,13,19] Epilepsy commonly attacks young adults in the most productive years of their lives and frequently leads to unemployment, which often confounds the problems not only of the afflicted, but also of the family that relies on their financial support.

Stigma and Discrimination

Epilepsy remains among the most stigmatized brain disorders.[13,20] The associated stigma is more obvious in developing countries because of illiteracy

Suggested Citation:"6 Epilepsy." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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and misinformation regarding the actual nature of the condition. The shame and fear associated with the disorder prevent many affected individuals from seeking treatment. As a result, their epilepsy becomes uncontrolled, with consequences for education, employment opportunities, and social acceptance.[5,21,22]

Children with epilepsy are removed from school and as adults lack the basic education needed for self-sufficiency.[22,23] Traditional medicines dispensed for epileptic seizures may be administered to children with febrile seizures with devastating consequences, such as oral burns and aspiration pneumonia.[24] Those afflicted also frequently suffer crippling malformations or death due to burns, drowning, or other accidents.[25] In Africa, for example, where open fires are used for cooking and heating, up to 30 percent of severe burns result from seizures. Because of the pervasive belief that epilepsy either is contagious or represents demonic possession, even family members may not act to pull these epilepsy sufferers from the flames.[18,26,27,28 and 29] Studies reveal that females with epilepsy are also less likely to marry and have children.[30] Consequently, these women are rejected by their families and often left to means of survival that include prostitution, which significantly increases their vulnerability to many sexually transmitted diseases, particularly HIV/AIDS.[18]

Treatment Gap

Even when proper medical treatment is sought and provided, patients do not recognize that long-term adherence to medications is required. The ensuing lack of adherence to treatment leads to seizure recurrences and a repetitive cycle of the social and physical burdens associated with the disorders. A treatment gap as high as 90 percent still affects many populations.[31,32] Other important factors contribute to the treatment gap, including cultural attitudes toward treatment, such as attributing the source of the illness to possession of the spirit or “the devil within.” Beliefs such as these provoke individuals to seek help from traditional healers and local religious figures [33,34 and 35] and do not lead them to effective medical treatments.[27]

Epidemiological studies reveal that the prevalence of epilepsy in developing countries is higher in rural than in urban populations. Reasons for this may include inadequate medical care facilities in remote areas for pregnancy control, safe delivery methods, early detection and treatment of childhood infections, and prompt and comprehensive health care.[27] Cultural factors such as ignorance, fear, and rural illiteracy (higher than among urban populations) lead to a delay in seeking early diagnosis and treatment and compound the burden of epilepsy in these poorer regions.

In developing countries, total earnings per capita per year amount to less than what one patient with epilepsy spends on treatment annually in developed countries. It has been calculated that the gross national product per capita of most developing countries barely suffices to buy a 2-year supply of

Suggested Citation:"6 Epilepsy." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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carbamazepine or valproic acid for one patient at the price at which it is sold in Europe. Therefore, monetary considerations often outweigh clinical judgment in therapeutic decisions.[34]

The availablity of anti-epileptic drugs (AEDs) in developing countries is limited because of poor drug production facilities and the inability of epilepsy sufferers to pay for the drugs. Indeed, it has been found that the developing countries, with 75 percent of the world's population, consume only 21 percent of the drugs produced globally, with drug consumption per capita being 12 times below that in the developed world.[33] Notable defects of the drug distribution systems in developing countries include a lack of suitable storage facilities, logistic coordination, and transportation, and a lack of midlevel management skills in inventorying, ordering, and stock control.[34] Poor quality control of domestically produced drugs may also be an important issue in developing countries.[33] The problems of drug supply, coupled with inadequacies in the systems for delivery of health care, prevent many from receiving the care they need.[33,34] For more information on the costs of treating epilepsy see Appendix D.

Infectious Diseases

A multitude of infectious diseases are risk factors for epilepsy. Rates of prevalence for these diseases remain high in developing countries and contribute significantly to the higher prevalence of epilepsy in these regions as compared with developed countries.[ 6]

Recommendation 6-1. To effectively address the needs of individuals with epilepsy and reduce the widespread stigma attached to the disease, national and local governments and health authorities of developing countries should support public education campaigns focused on the causes of epilepsy, the impact of the disease on the afflicted, and the availability of safe and effective treatments. Additionally, the rights of individuals with epilepsy under adequate treatment should be enforced to allow them equal access to employment, driving, and marriage.

PREVALENCE AND INCIDENCE

A number of recent neuroepidemiolgical studies provide fairly accurate data on the prevalence and incidence of epilepsy in various geographic regions of the world (see Table 6-2 and Table 6-3).[1,2,3 and 4,7,8,9,10 and 11,36,37,38,39,40 and 41] However, the comparability of these data is limited because of the lack of consistency in diagnostic definitions and methodology. Additionally, local variations in the prevalence of risk factors and genetic factors that may predispose individuals to develop epilepsy have undoubtedly contributed to the marked heterogeneity in epilepsy prevalence and incidence throughout the world.[11,40,41 and 42]

Suggested Citation:"6 Epilepsy." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
×

The available community-based prevalence data on epilepsy are rather consistent for industrialized countries. The prevalence rates range from 3.3/1000 population in England to 6.6/1000 in the United States.[ 17] Studies in developing countries reveal much higher rates: 17/1000 in Ecuador,[1] 26–40/1000 in Liberia,[43] and 20/1000 in Tanzania.[38] The People's Republic of China (PRC) reports a rate of 4.6/1000 [2] and some areas of Uganda have recorded rates as high as 57/1000.[ 44]

A number of epidemiological studies have been conducted in India during the last three decades to determine the prevalence of epilepsy.[ 45,46] Careful scrutiny of the methodology and analysis of these studies reveals that 12 of them included house-to-house surveys with sound methodology and are comparable. The studies were conducted in various regions of India, representing populations from the north, south, east, and west of the country. They included both urban and rural populations. The prevalence rate of epilepsy was found to be 2.2 –9.0/1000 population. A recent house-to-house survey included a large sample (102,557) of Bangalore urban and rural populations and showed a prevalence rate of 8.8/1000. The prevalence rate in the rural population was 11.9/1000 and in the urban population was 5.7/1000, highlighting the fact that the prevalence of epilepsy is two-fold higher in rural than in urban populations.[47] This large urban–rural difference calls for further case control studies to determine the risk factors involved, such as infections, trauma, obstetric practices, availability of health care facilities, and attitudes toward epilepsy.

TABLE 6-1 Prevalence rate of epilepsy in Africa (per 1,000 inhabitants)

Country

Inclusion Criteria

Prevalence Rate

Sampling Size

Method

Burkina-Faso [48]

RS

10.60

16,627

Community-based

Ethiopia [49, 50]

 

5 (urban)

3,700

Community-based

   

8 (rural)

 

Community-based

   

5.20

60,820

Community-based

Ivory Coast [48]

RS

7.60

1,176

Community-based

Liberia [51, 52]

RS

28.00

4,436

Community-based

   

43.00

2,733

Community-based

Nigeria [37, 53, 54]

 

3.01

2,592

Community-based

 

RS

37.00

903

 
 

RS + EEG

5.30

18,951

 

Senegal [55]

Generalized seizures

3.10

35,219

Community-based

South Africa [48]

RS

0.22–2.20

50,000

Community-based

     

36,700

Mine workers

Tanzania [56]

RS

20.00

10,000

Community-based

Togo[57]

RS + EEG

2.30

19,241

Community-based

 

RS

19.8

9,143

 

Zimbabwe [58]

 

7.40

17,500

Community-based

Suggested Citation:"6 Epilepsy." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
×

TABLE 6-2 Prevalence rate of epilepsy in Latin American countries

Study

Country

Prevalence RateA

Population

Year

Buenos Aires [59]

Argentina

3.7

6,194

1995

Bogota [60]

Colombia

19.5

8,970

1978

Cangahua [40]

Ecuador

14.3

72,121

1984

Changuinola [61]

Panama

57.0B

337

1988

Cordillera Province [62]

Bolivia

24.5

10,000

1999

Coyocan [63]

Mexico

16.0

1,013

1980

El Salvador [64]

Chile

17.7B

17,694

1988

Marianoa [65]

Cuba

7.5

14,445

1980

Medellin [66]

Colombia

21.4

4,549

1988

Melipilla [67]

Chile

27.6

2,085

1975

Migues [5]

Uruguay

9.1

1,975

1990

Palugillo [7]

Ecuador

22.6

221

1997

Porto Alegre [5]

Brazil

16.5

 

1997

Quiroga [1]

Ecuador

17.1

1,113

1985

Rural and urban population [5]

Colombia

13.2

9,800

1991

Sao Paulo [68]

Brazil

11.9

 

1986

Tecomatian [69]

Mexico

25.0–41.6

360

1975

Tlalpan [70]

Mexico

42.2

2,027

1976

V. del Cerro (present study) [5]

Uruguay

11.5

21,186

1993

Viacha(33)

Bolivia

26.2

1,183

1985

Z. Subtropical (23)

Ecuador

16.6

1,382

1984

A Per 1,000 inhabitants; includes active and nonactive epilepsy

B Includes only active epilepsy

The prevalence of epilepsy in developing countries increases with age, reaching a peak in the third and fourth decades. It is interesting to note that in developing countries, the prevalence rate diminishes among those aged 60 and above. This fact may be explained by the increased mortality of patients with epilepsy, spontaneous remission, and the low survival of individuals with seizure disorders due to stroke and brain tumors. Only in Rochester, Minnesota, in the United States has the population above age 60 shown an increased prevalence rate, probably reflecting the improved medical care and follow-up of such individuals.[17] As with the other age groups, the prevalence of epilepsy among children is highest in the most deprived areas of the world.[71]

Information on the incidence of epilepsy is widely available for developed countries, but the same information for developing countries is less complete. Reported figures range from 145/100,000 population per year for Japan [72,73]

Suggested Citation:"6 Epilepsy." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
×

to 48/100,000 per year in the United States.[28] Rates ranging from 109—190/100,000 per year have been reported for Ecuador.[12,74,75] Rates in Africa have ranged from 64/100,000 in Ethiopia [9] to 156/100,000 in Uganda.[44]

Community-based surveys have proven to be an effective method for evaluating the magnitude and distribution of the disease.[15,16] However, the results of such surveys are influenced by local cultural factors. If epilepsy carries a social stigma, which is commonly the case, patients suffering from the condition will be hidden from researchers by family members. Because of the difficulties and the expense of implementing door-to-door surveys, increased attention is being focused on the use of key community informants to identify patients suffering from epilepsy.[41,76,77 and 78] This strategy was applied successfully, for example, in an urban marginal and rural region in Kenya.[33]

Mortality Rates

It is well known that mortality data based on the single cause of death listed on a death certificate often underrepresent the number of deaths due to predicating conditions such as epilepsy. Case fatality rates for epilepsy are low in developed countries, so that mortality statistics are not a good indicator of the frequency of the disease.[ 4] A community-based study done in Ethiopia revealed that 6.3 percent of patients with epilepsy had died over a 2-year period as a results of complications from the disease.[9] In Africa, epilepsy mortality has been shown to be related to status epilepticus, falls, drowning, suicide, and burns.[79] More research is needed to adequately understand this aspect of epileptic disease burden.

RISK FACTORS

Data collection on the epidemiology, etiology, and natural history of epilepsy have increased understanding of this devastating disease. Many of the risk factors for epilepsy have been identified, and understanding of their relative contribution to epilepsy incidence continues to improve.[19,80,81,82,83 and 84] It will be important for the development of efficacious and comprehensive programs for the prevention and treatment of epilepsy to further investigate and identify risk factors in developing country populations.

More recently, researchers have emphasized the importance of studying risk factors separately according to the different epilepsy types. It has also been stressed that taking into account the age of onset of epileptic disorders will increase study group homogeneity, therefore increasing the potential for identifying specific risk factors.[ 12,74,85,86]

Suggested Citation:"6 Epilepsy." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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Genetic

The risk of epilepsy is increased three-fold for individuals who have a first-degree relative with the condition.[87] In addition, a number of diseases that follow Mendelian patterns of inheritance may have seizures as one of their manifestations or their only manifestation. In many developing countries, consanguinity is relatively common. Such practices are likely to increase the risk of seizure disorders in any offspring. In isolated communities, specific inherited diseases may contribute to the etiology of epilepsy, as is the case in the Grand Bassa Country of Liberia and among the Wapagoro tribe in Tanzania.[43,88] However, a studied conducted in the Parsi community of Bombay showed no significant association between consanguinity and epilepsy despite the high frequency of consanguinious marriages.[81]

Pre-, Peri- and Post-Natal

In a community-based study in Ecuador,[12] significant risk factors for epilepsy starting before age 20 were found to be a positive family history (genetic factors), prematurity, perinatal hypoxia, sleep disorders in the first 3 months of life, and febrile seizures; for epilepsy starting at age 20 and above, only prematurity was found to be a significant risk factor. When the analysis was done according to seizure type, it was found that for generalized seizures, family history and febrile convulsions were significant risk factors, whereas for partial seizures, family history, prematurity, perinatal hypoxia, and sleep disorders were statistically significant factors.[12,74] Perinatal hypoxia is associated with epilepsy in developing countries as it relates to maternal and childhood malnutrition. In an Ecuadorean study, calculation of the population rate difference percentage suggested that programs aimed at controlling both prematurity and perinatal hypoxia could decrease the number of epilepsy cases by 42 percent.[ 12,74] In the PRC, carefully designed epidemiological studies found that the following were significant risk factors for idiopathic epilepsy: premature or difficult birth, maternal disease during pregnancy, febrile convulsions, family history for epilepsy, and maternal age above 30.[2,84] In Nigeria, the putative risk factors for epilepsy were found to be febrile convulsions, malnutrition, maternal alcohol consumption, and lack of immunizations.[37,83]

In developed countries, where acquired epilepsy constitutes about 40 percent of all cases, perinatal pathology is reported to be the cause of around 14 percent of all epilepsies.[85] In developing countries this figure should be higher, although there are no good community-based studies to provide such data. The causes of perinatal hypoxia include maternal cardiovascular disease, placental and umbilical cord disorders, prolonged labor, and airway obstruction at birth. In dystocic deliveries, the excessive reduction of fetal cranial diameter may lead to herniation of hippocampal regions through the tentorium, causing

Suggested Citation:"6 Epilepsy." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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ischemia, atrophy, and subsequent gliosis of these structures (mesial sclerosis). These conditions in turn predispose to epilepsy and can now easily be visualized by magnetic resonance of the brain in individuals thus affected.[11,86,87]

In many developing countries, most deliveries in rural areas are performed by traditional birth attendants. Complications with delivery are common, and the incidence of preterm deliveries is at least twice that in developed countries.[89] Mothers in developing countries are frequently malnourished, anemic, and exposed to a variety of infections that could affect the baby in utero or at delivery and increase the risk for epilepsy.[19,86]

Parasitic Infections

Neurocysticercosis is caused by Taenia solium (more commonly known as tapeworm). This disease may account for up to two-thirds of late-onset epilepsy (epilepsy starting above age 20) in geographic regions in Africa, Asia, and Latin America in which this infection is endemic.[90,91,92,93,94,95,96,97 and 98] Rapid control of transmission of T. solium taeniosis from animal to human may be attained through a vaccine that renders pigs immune to cysticercosis.[99] (Additional information on neurocysticercosis as a risk factor for epilepsy and the implications for prevention and treatment can be found in Annex 6-1.)

Paragonomiasis, caused by the parasite Paragonimus westermani, is endemic to Asia, particularly Korea, Japan, the Philippines, and China, as well as some parts of Africa and South America. Epileptic seizures, usually focal motor, are a common manifestation of this condition.[11,100,101]

Schistosomiasis can also induce seizures. This is the case particularly with S. japonicum infections, and less commonly with S. mansoni and S. haematobium infections. Acute schistosomiasis may produce a serious encephalopathy with coma, papilledema, and partial or generalized seizures. Chronic forms of cerebral schistosomiasis, caused by embolized schistosoma eggs, are commonly manifested in epileptic attacks.[102]

Congenital toxoplasmosis, acquired during pregnancy, induces seizures in 40–60 percent of affected children, who may display mental retardation and blindness as well.[103104] Toxoplasmosis is also a frequent opportunistic infection in patients with acquired immunodeficiency syndrome (AIDS), inducing seizures in about 25 percent of affected individuals.[105]

African trypanosomiasis, or sleeping sickness, is caused by T. brucei, and is widely distributed through sub-Saharan Africa. The chronic stage of the disease is characterized by progressive neurological involvement, including partial and generalized seizures.[106]

Chagas disease, caused by T. cruzi, is a public health problem in rural areas of Central and South America. Cerebral involvement is secondary to embolization of the parasite and manifests itself as a late-onset epilepsy, involving mainly partial seizures.[107]

Suggested Citation:"6 Epilepsy." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
×

Malaria is endemic to tropical Africa, Latin America, and Asia. Epilepsy is a late sequela of this common disease. Status epilepticus has been reported to occur in up to 13.6 percent of malaria cases. One-third of these occurrences are due to infection with Plasmodium falciparum, which produces the dreadful cerebral malaria.[87,105]

Epilepsy can also be a rare manifestation of other parasitic infections of the central nervous system, such as sparganosis [108,109] and onchocerciasis.[44,110,111]

Bacterial Infections

Tuberculous meningitis is highly prevalent in urban marginal and poor rural areas of most developing countries, but it is particularly important in Asia and certain African countries.[112,113 and 114] This infection can cause epilepsy as a late sequela in 8–14 percent of affected patients. Intracranial tuberculomas can present as space-occupying lesions and seizures.[115,116 and 117]

Pyogenic meningitis is also a common infection in the tropics, and epidemics of meningococcal meningitis occur periodically in Brazil and sub-Saharan Africa. In the United States, the overall risk for epilepsy was found to increase seven-fold among 734 survivors of intracranial infections; for individuals with a diagnosis of brain abscess, the risk was more than 40 times greater. The risk for epilepsy remains elevated in patients who have suffered from meningeal infections for at least 20 years after the illness.[118]

Viral Infections

Japanese encephalitis is perhaps the most important and best-documented form of epidemic viral encephalitis in developing countries.[119,120 and 121] Bangladesh, India, Nepal, Thailand, and Vietnam are the most affected areas. Epilepsy is a frequent manifestation, found in 1–20 percent of survivors.[122,123]

Human immunodeficiency virus (HIV) is often accompanied by seizure disorders. Up to 60 percent of patients with HIV in Africa have been diagnosed with epilepsy.[124] The rising epidemic of HIV/AIDS in Africa may soon be the leading cause of seizure disorders.

Head Injuries

In the United States severe head trauma accounted for 12 percent of epilepsy cases.[125] Annegers et al. found the risk slightly higher at 17.2 percent.[ 126] Head trauma related to road traffic accidents or violent assault is a very common cause of epilepsy in Brazil and Uruguay.[103,127] Occupational hazards and accidental falls due to poor safety conditions may also result in head injuries.[128,129,130 and 131] Head trauma is a preventable condition, and campaigns to

Suggested Citation:"6 Epilepsy." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
×

reduce car and motorcycle accidents and other causes of these injuries may assist in reducing the occurrence of epilepsy.

Febrile Seizures

Febrile seizure is defined as an event in infancy or childhood, usually presenting between ages 3 months to 5 years, associated with fever, but without an intracranial infection or other defined cause. Febrile seizures occur in 2–4 percent of children, but rates as high as 14 percent have been reported in selected populations. Untreated fevers that lead to febrile seizures can increase the risk of developing epilepsy; however, studies show a low range of occurrence (from 1.5 –7 percent) of epilepsy from febrile seizures.[81,132] The association between febrile seizures and later epilepsy are strong in studies from both developed and developing countries, however, the cause of this association remains unclear.[17,81,83] It is important to note that in areas where malaria is endemic, a child presenting with a febrile seizure may be harboring the plasmodium parasite. In some regions of Africa, 60 percent of seizure disorders seen in general hospitals in the first 6 years of life are related to malaria.[19,81,82 and 83,86]

INTERVENTIONS

Prevention

Many of the risk factors for epilepsy described in this chapter are preventable or modifiable. Such preventative measures could significantly reduce the incidence and prevalence of epilepsy in developing countries. Prevention programs that include the following components are recommended by this committee and included in WHO manuals for the primary prevention of epilepsy [133]:

  • Prenatal care—immunization of pregnant women, improvement of mothers' nutritional status, detection of high-risk preganancies, and control of infectious diseases during pregnancy.

  • Safe delivery—avoidance of labor and delivery complications, labor surveillance, and detection and urgent treatment of neonatal hypoxia.

  • Fever control in children—avoidance of febrile illnesses in children, especially those prevented by vaccines; control of increases in temperature by antipyretic drugs or physical cooling agents such as baths; and neurological consultation and treatment if the child presents with recurrent febrile seizures.

  • Reduction of the causes of brain injury—promotion and enforcement of traffic regulations and speed limits, legal punishment for drunken driving, compulsory use of seat belts and safety seats for children and of helmets for riders of bicycles and motorcycles; at work, use of helmets, safety cords, and adequate lighting; at home, elimination of angular structures located at a child's head level, safety precautions on stairs, and window safety systems;

Suggested Citation:"6 Epilepsy." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
×

and avoidance of neurotoxic agents, such as alcohol for pregnant mothers, lead, and pesticides.

  • Control of infectious and parasitic diseases—extension of vaccination programs, mainly against diphtheria, pertussis, tetanus, measles, and tuberculosis, to the whole target population; environmental control of parasitic diseases, such as cysticercosis and malaria; and detection and treatment of responsible vectors.

  • Genetic counseling—accurate medical information about the risk to offspring when one or both parents have epilepsy.

Control of environmental and genetic conditions and management of human and animal infections will continue to lead to significant reduction in the burden of epilepsy in developing countries. For example, where T. solium infection is endemic, up to 50 percent of all cases presenting with epilepsy are caused by cysticercosis. Strategies to reduce the impact of this condition in communities may include affordable blood tests that can be used to diagnose patients suspected of harboring these parasites, with safe and effective drugs administered to treat them along with medical and veterinary services working together to reduce the transmission of this infection from animals to humans.

Initiatives to prevent epilepsy clearly require effort from multiple sectors within local and national infrastructures. In addition to health care providers, teachers, community leaders, sanitation and transportation personnel, legislators, and the media can play an important role in implementing control measures and educating communities about the prevention of epilepsy.

Treatment

In the face of financial and organizational constraints, the choice of drug for the primary therapy of epilepsy in developing countries assumes great importance. Phenobarbital and phenytoin are the most cost-effective drugs available for the treatment of epilepsy and prove effective in 70 percent of all cases.[134,135,136 and 137] In India, these two drugs are the most commonly used AEDs, being administered to up to 93 percent of epilepsy patients.[138]

Phenobarbital is recommended as the first-line drug for the treatment of partial and generalized tonic-clonic epilepsies in developing countries.[31,32,33 and 34,76,135,139,140,141 and 142] Use of this old and simple drug is encouraged because of its efficacy for a wide range of seizure types and its low cost makes it suitable for use in primary health care in developing countries. Although WHO findings on the acceptability of phenobarbital were established through extensive consultation with neurologists and other specialists working in developing countries, the suitability of phenobarbital as an AED for children raised considerable concern among developed-country specialists, who contended that the drug's side effects, especially behavioral problems such as hyperactivity, might contraindicate its use.[19,143] These concerns were dismissed, however,

Suggested Citation:"6 Epilepsy." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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by randomized controlled trials conducted to assess the acceptability and safety of phenobarbital for childhood epilepsy.[134,135 and 136,144] New evidence on the use of phenobarbital at the community level by primary health care personnel, compared with use of both phenytoin and carbamazepine, has established phenobarbitol as the drug of choice for initial treatment of partial and generalized epilepsies in primary health care settings.[31,32,33 and 34,139,140 and 141,145]

A price comparison for AEDs in six developing countries of South America showed wide variation. Phenobarbital, for example, costs only US$1.50 per monthly treatment in Colombia, and up to US$10.00 in Brazil. Similarly, phenytoin treatment costs US$1.15 per month in Venezuela and US$17.00 in Uruguay.[140] An interesting comparison conducted in Colombia, South America, demonstrated that traditional herbal treatments for epilepsy are six times more expensive than pharmacological treatment (US$2,210 vs. $364), taking into account the indirect costs of being jobless and the family expenditures required to care for epilepsy patients who continue having seizures while subjected to ineffective therapies.[ 140]

Primary Care. The use of primary health care workers and key community informants to identify and follow patients under treatment with either phenobarbital or phenytoin appears to be the most cost-effective intervention for reducing the treatment gap for epilepsy in developing countries. Pilot projects conducted in Asia, Africa, and Latin America using this primary health care strategy in urban marginal and rural areas have demonstrated its safety and feasibility.[31,76,113,146,147 and 148] Through use of these two inexpensive medications, up to 80 percent of patients presenting with generalized tonic-clonic seizures could be brought under control.[12,32,136,137,149]

In addition to administering and monitoring of drug treatments, trained primary care health workers can help to identify individuals with epilepsy in their communities and encourage them to seek medical attention. They can play an equally important role as health educators by providing accurate information about prevention, causes, and available treatments of epilepsy. Greater understanding of epilepsy has been shown to improve attitudes toward treatment and reduce stigma.[33,145,150,151 and 152]

Epilepsy surgery. A recent study conducted in Colombia presents evidence that surgery is a cost-effective treatment option for epilepsy patients in developing countries.[153] Twenty-six developing countries currently conduct epilepsy surgery, and available data suggest that outcomes achieved are similar to those in developed countries, but obtained at a fraction of the cost.[ 54] The advantages of surgery in selected cases of clinically intractable epilepsy and the possible early use of surgery to avoid more expensive, life-long pharmacotherapy may indicate that this is a cost-effective alternative for resource-poor settings capable of supporting the necessary technology and medical training.[12,154] The establishment of additional epilepsy surgery centers in developing countries will require collaborative support from research and clinical institutions.[11,155]

Suggested Citation:"6 Epilepsy." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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BOX 6-2 Model for managing epilepsy in Malawi

In Malawi, as in many developing countries, people with epilepsy travel to various traditional healers seeking treatment or a cure. These traditional healers often encourage patients to ingest a mixture of roots that precipitates purging or vomiting. Unless they are suffering from burns sustained during an epileptic seizure, patients rarely seek care at a hospital. Through community publicity and education about the availability of biomedical treatment, a program sought to encourage and promote individuals suffering from epilepsy in rural Africa to seek regular care at a hospital or health center.

After the first eight months 11 patients were attending the hospital for treatment. After an area action committee conducted a targeted information campaign, 70 more patients were receiving treatment after three months. Because many of the patients walked great distances to gain treatment, two mobile clinics were established by linking with an existing mobile health program for children under five years of age. After two years 461 patients were registered in the program. Of the 254 patients treated for epilepsy in the first 18 months, 68 percent continued treatment beyond six months. Among those same individuals, 56 percent no longer suffered seizures—showing significant improvement over the pre-treatment occurrence of one seizure per month in 88 percent of this group.

In the hospital and mobile clinics, diagnosis was based on seizure history and use of a modified form of the revised ILAE classification. Electroencephalography and CT scanning were not available. Only patients having two or more seizures in a year were treated with anticonvulsants. Simple explanatory models were used during the first visit with patients and family members. Descriptions of the disease and treatments included:

  • Epilepsy is due to a scar on the brain, sometimes caused by meningitis, sometimes following cerebral malaria, sometimes inherited. Treatment aims to stop seizures from occurring in order to allow the scar to heal.

  • It takes a long time for the scar to heal, and we would not consider reducing, and possibly discontinuing treatment for at least two years.

  • Seizures will not stop immediately. The medicine needs time to work effectively. It may take several months to determine the dose of drugs needed for each patient. Patients should not become discouraged during this time.

  • If side effects such as a rash occur the patient must stop taking the drug immediately and report to the hospital.

  • Alcohol should be avoided, yet no other restrictions for diet are recommended.

Phenobarbitone and phenytoin were the only medications used because of their availability in the community and suitability for administration by trained nurses or community health workers who were familiar with their use. The population of the region was largely subsistence farmers; therefore, it was determined that medication must be provided free of charge to enable adequate treatment.

Suggested Citation:"6 Epilepsy." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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Record cards were distributed to patients to remind them of the next scheduled treatment, to track medication dosage, and to record the numbers of seizures between visits to the hospital or clinic. For the patients, the record cards clearly illustrated the number of tablets to be taken daily. The supervising physician and nurses and community health workers were able to use the information from the cards to determine any needed changes to drug treatment or dosing frequency.

Publicity in communities through widely known organizations or individuals was instrumental in the initial registration of patients and for maintaining their adherence to treatment. After an article profiling the program appeared in a national medical journal, more district and community health centers moved to establish similar models. As additional programs were developed, the following guidelines were created for the management of epilepsy in community health centers:

  • publicize the availability of treatment;

  • educate patients and staff;

  • use simple anticonvulsant regimens with phenobarbitone or phenytoin;

  • maintain adequate supplies of drugs;

  • offer drugs at no charge;

  • conduct monthly review clinics with a physician;

  • ensure patient always sees the same health worker; and

  • use mobile clinics.

As a result of the promotion of these guidelines, the number of patients seeking treatment at the hospitals and designated clinics increased significantly. These findings suggest that people with epilepsy can overcome the myths and mistaken beliefs about the disease allowing health programs for the effective treatment of epilepsy to be adopted and administered in rural areas of the developing world.

In recognizing the financial limitations and lack of medically trained professionals in the region, the program design sought to balance efficacy with simplicity of use. From 1980 to 1998 in Malawi no change in the physician to patient ratio of .05 per 1000 people was experienced. Therefore, the program relied heavily on the use of trained nurses and community health workers.

The success of the Malawi model provides a useful framework for other communities; however, limitations in the sustainability of the program must be noted. Delivery of effective care through this program greatly diminished upon the departure of the founding physician from the country. Clearly community knowledge and education about available treatments for epilepsy were essential to the program; however, future efforts would benefit from a better understanding of community attitudes toward epilepsy and health care that could be gained by engaging not only primary health care centers but also important groups such as religious, political, and social leaders. A wider community-based approach may lead to long-term, vested interest in the success and continuation of the programs.

Source: [145,152]

Suggested Citation:"6 Epilepsy." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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Recommendation 6-2. Demonstration projects for developing primary health care programs and interventions for the prevention, diagnosis, and treatment of patients suffering from generalized tonic-clonic seizures should be implemented. These projects should incorporate and evaluate the established WHO guidelines for prevention and the use of first-line anti-epileptic drugs, such as phenobarbital, phenytoin, carmabazepine, and valproic acid.

Recommendation 6-3. With the support of international, national, and local governments and non-governmental organizations, demonstration programs in 4–6 countries of Latin America, Africa and Asia, where T. solium teniasis and cysticercosis are endemic should be established, in order to drastically diminish active transmission of this infection and to monitor the effectiveness of such programs in the medium-and long-term on decreasing epilepsy incidence in humans and abolishing this parasitic infection in pigs.

Recommendation 6-4. Tertiary medical centers with the medical and technical expertise required for epilepsy surgery should establish such surgical centers. Assessment of the required surgical training and medical equipment should be in collaboration with surgical centers already established in developing countries and centers in developed countries. Financial and technical support from developed country institutions will be important.

The range of social, economic, and medical consequences associated with epilepsy, along with the availability of cost-effective methods of treatment that are efficacious in up to 70 percent of treated patients, is the most compelling reason for this disease to receive high priority in public health planning and education.

CAPACITY

Training

An important strategy for control of epilepsy in developing countries may be training PHCWs (see Box 6-3).[40,150,152] In developing countries, trained neurologists are scarce and cannot cope with the huge tasks of diagnosis, treatment, and surveillance of patients with epilepsy, especially in rural areas.[149,157,158] Even general medical practitioners are often unavailable in rural regions that contain communities of less than 1,000 inhabitants each, separated by long distances and poor road conditions. The role of medical specialists and general practitioners will be essential for conducting appropriate training, developing safe and cost-effective protocols for pharmacotherapy, confirming diagnosis, initiating treatment, and overseeing the operation of general medical clinics and community health care centers (see Box 6-3).[12,76,136]

Suggested Citation:"6 Epilepsy." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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Nurses, medical technicians, and trained primary health care workers have proven to be very helpful in managing patients with epilepsy. When provided with appropriate training and supervision, they are able to oversee the course of treatment for patients in remote areas, which includes the monitoring of blood levels for toxicity during pharmacotherapy and attention to other possible drug side effects.[ 76,149,157,160,161] Community mental health and social workers can often assist patients and families in coping with the social, financial, and psychological consequences of the disease.[162]

BOX 6-3 An Epilepsy Treatment Program for Primary Health Care Workers in Ecuador

In 1987 the government of Ecuador agreed to sponsor a pilot project to study the feasibility of using an informal health system, comprising a community and its primary health care workers (PHCWs), to identify, treat, and control patients suffering from tonic-clonic seizures, the most frequent and easy-to-treat epilepsy type. The PHCW was a member of the community who had received 6 months of training in basic skills needed to diagnose and treat the most common medical illnesses in his/her community. A 3-day course presented by trained neurologists enabled the PHCWs to detect cases of epilepsy and to use phenobarbital for their control, following strict algorithms developed by specialists in the urban university hospital center.[ 140,141,144] In one community, the PHCW identified and treated 16 patients with generalized tonic-clonic epilepsy. In a control community, 12 patients were treated by a fully trained neurologist. Eight patients in the first group and 7 in the second completed the 12-month study. Compliance and side effects were comparable in the two groups. No difference was seen among patients treated by the PHCW and the neurologist. The PHCW was able to use the protocols for epilepsy detection. Although the diagnosis was confirmed by a physician, the PHCW was capable of administering the phenobarbital and managing its side effects. Moreover, the PHCW was able to obtain the patients' confidence throughout the treatment period and to help them adjust within the community.[ 141]

Results of this study and others indicate that the use of PHCWs for the identification, treatment with low-dose phenobarbital, and surveillance of patients with generalized tonic-clonic epilepsy is feasible and practical in remote communities where medical expertise is difficult to obtain or nonexistent. This strategy may help millions of patients with epilepsy in rural areas of developing countries who currently receive no treatment.

Suggested Citation:"6 Epilepsy." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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BOX 6-4 Use of District-Level Doctors (India)

A review of neuroepidemiological surveys conducted in different regions of India indicates that nearly 8 to 10 million people have epilepsy. With the wide gap between available trained neurologists (550) and the projected minimum required (5,000), alternative strategies to provide care for people with epilepsy need to be developed. WHO has promoted care of persons with epilepsy as part of primary health care in developing countries since 1975.[159]

In India, integration of mental health care with primary health care has included epilepsy as one of the prorities, along with psychoses, depression, and mental retardation, since 1975. Training manuals and materials have also been developed and evaluated.[163,164] Pilot programs covering populations of 40,000 to 2 million have shown the feasibility of care of epilepsy by primary care doctors. A concept for a national Epilepsy Control Programme has been developed following a series of workshops funded by WHO. One of the key elements is to train district medical officers (physicians and pediatricians) in the diagnosis and management of epilepsy.

In the 25 states of the country, there are nearly 500 districts, with an average population of 1.5 to 2 million in a district. District-level medical officers and administrative staff are responsible for implementing, executing, and monitoring various health programs at the level of primary health centers and taluks (regional governments) under their jurisdiction.

District medical officers are given training on indentification, diagnosis, and drug treatment. They are also provided insight into psychosocial issues, such as education, marriage, and employment, related to epilepsy. The importance of compliance by patients and continuous availability of a free supply of commonly used anti-epileptic drugs has been emphasized. The district medical officers have also been motivated to conduct outreach epilepsy clinics involving the primary health center (PHC) doctors and to train PHC doctors in the diagnosis and treatment of epilepsy. This strategy will facilitate networking of epilepsy. The training program was conducted as a 2-day workshop.

Neurologists with special interest and expertise in epilepsy formed the resource faculty. Fifty-seven district medical officers drawn from 10 states have already completed the programs. During the training a standardized validated questionnaire covering the various elements of the training were administered to the district medical officers. Pre- and post-training analysis has shown that the training program had significant impact (70–80%) on the knowledge and skills in the management of epilepsy.

It is planned to extend this program to cover all the districts in the country by identifying nodal neurologists in the different states who in turn would supervise the epilepsy control program.

Source: [164]

Suggested Citation:"6 Epilepsy." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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Research

Despite the difficulties in gathering data on epilepsy discussed earlier in this chapter, WHO has been successful in sponsoring a worldwide initiative to obtain epidemiological data on epilepsy, specifically from developing countries where such information was incomplete or lacking.[1,2 and 3] Use of the Protocol for the Epidemiological Investigation of Neurological Disorders in Developing Countries, developed by WHO more than 15 years ago, made it possible to gather data on the disease from Africa, Latin America, and Asia, and to compare it with data from Europe and North America.[15] The results made clear to the world that epilepsy was a significant public health problem in the majority of the investigated geographic areas and prompted the World Health Assembly to sponsor the Initiative To Help People with Epilepsy.[165]

The full picture of the epidemiology of epilepsy remains inconclusive. Research is needed to ascertain specific risk factors for the development of the disease, particularly in developing-country environments. Genetic causes should be explored in various geographic locations and among different ethnic groups. Such research would improve the cost-effectiveness of efforts for prevention and treatment. The findings from such efforts could have an impact in both developed and developing countries.

In 1997, three international organizations—WHO, the International League Against Epilepsy (ILAE), and the International Bureau for Epilepsy (IBE)—joined forces to initiate the Global Campaign Against Epilepsy (GCAE). The strategy of the GCAE includes two parallel and simultaneous tracks: (1) raising of general awareness and understanding of epilepsy, and (2) support for departments of health in identifying needs and promoting education, training, treatment, services, research, and prevention nationally. One of the main activities within the second track of the GCAE is development of demonstration projects, being carried out in a number of countries in Africa, Asia, and Latin America. The objectives of the demonstration projects are:

  • To reduce the treatment gap and the physical and social morbidity of people suffering from epilepsy through intervention at the community level;

  • To train and educate health professionals;

  • To dispel stigma and promote a positive attitude toward people with epilepsy in the community;

  • To identify and assess the potential for prevention of epilepsy; and

  • To develop a model for promotion of epilepsy control worldwide and for its integration into the health systems of participating countries.

Through this program a questionnaire designed to standardize data collection methodologies has been developed in collaboration with the Institute of Neurological Epidemiology and Tropical Neurology of Limoge (France) and the

Suggested Citation:"6 Epilepsy." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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Pan-African Association of Neurological Sciences.[166] The estimated duration of this project is 5 years.

The availability of human and technical resources for medical assessment of patients with epilepsy differs widely among developing countries, as well as between urban and rural areas within a country. Training of personnel at all levels of intervention for patients with epilepsy is a principal requirement for the success of any initiative aimed at helping these individuals.[147] Educational programs for professionals and patients must be based on perceived local needs and differing social and cultural conditions. Multiple levels of international, governmental, and nongovernmental organizations could assume an important role in this effort, as could national centers for training and research that included epilepsy as a priority disease on their research and planning agendas (see Chapter 3 and Chapter 4 for more information on nationals centers for training and research).[ 19,80,81,82,83 and 84,147,167]

In this context, it is important that GCAE be enlisted by all national governments and local communities in developing countries attempting to address the burden of epilepsy to accomplish the following objectives:

  • To increase public and professional awareness of epilepsy as a universal, treatable brain disorder;

  • To raise epilepsy to a new plane of acceptability in the public domain;

  • To promote public and professional education about epilepsy;

  • To identify the needs of people with epilepsy on a national and regional basis; and

  • To encourage governments and departments of health to address the needs of people with epilepsy, including awareness, education, diagnosis, treatment, care, services, and prevention.

Recommendation 6-5. Guidelines for training and treatment protocols should be established by national centers of training and research. Where possible, these centers should work in conjunction with the WHO/ILEA/IBE Global Campaign Against Epilepsy. These centers should be informed by local epidemiological research and should reflect the needs of the population.

Specific programs of operational research for implementing training, prevention, and treatment should include the following:

  • Specialists and general practitioners who are well-informed about current knowledge on the management and prevention of epilepsy and sensitized to the cultural attitudes within their societies that will impact the training they provide to other levels of health care personnel.

Suggested Citation:"6 Epilepsy." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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  • Training of nurses who can appropriately supervise PHCWs and monitor the treatment outcome of patients in community-based, primary health care centers.

  • Training of primary health care personnel and key community informants that will enable them to counsel their communities on methods of preventing epilepsy and to identify and administer the treatment of patients with epilepsy at the community level.

  • Training surgery teams to function in selected major cities of developing countries where the necessary equipment can be maintained.

  • Adequate drug supplies and means of distribution

  • Methods for surveillance that provide data collection for:

    • Cost-outcome analyses that provide government officials and funding agencies the information needed for health planning and continued program development;

    • Quality-of-life and disease burden measurements for epileptic patients; and

    • Socioeconomic determinants of the outcome measures that could best reflect optimal care for epilepsy patients in developing countries.

Recommendation 6-6. Research on the causes of epilepsy and the outcomes of treatment are needed in developing countries. Collaborative research between national centers and research centers in developed countries should be supported.

Collaborative research should include but not be limited to the following investigations:

  • Risk factors for epilepsy related to infectious diseases that remain common and endemic in most developing countries;

  • Exploration of genetic risk factors for epilepsy among different geographic and ethnic populations;

  • Nutritional status, genetic factors, and dietary factors that will affect dosage recommendations for AEDs; and

  • Immunological research directed at developing a cost-effective vaccine against porcine and, eventually, human cysticercosis.

Suggested Citation:"6 Epilepsy." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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ANNEX 6-1

Neurocysticercosis

The parasitosis produced by Taenia solium, the pork tapeworm, is recognized as one of the leading causes of epilepsy in the developing world. When the larval stages of this parasite, cysticerci, invade the human brain, the resulting neurocysticercosis (NCC) induces epilepsy in a high proportion of cases, and is now being diagnosed in numerous countries throughout Africa, Asia, and Latin America, where this zoonosis still constitutes a serious public health problem.[79,80,90,97] In these studies, up to 50 percent of epilepsy cases have been shown to have cysticercosis as a putative factor.

NCC is highly prevalent in communities with poor sanitation, the crowded coexistence of humans and animals, and a lack of adequate water and sewage systems. Recently, NCC has been recognized in industrialized countries with increasing frequency, the result of both migrant infected populations and locally acquired cases.[168,169,170,171 and 172]

BIOLOGICAL CYCLE

The biological cycle of this parasite involves an intermediary host, the pig, which becomes contaminated with Taenia solium eggs contained in feces of infected humans. These eggs then invade the pig's tissues, hatching into larvae known as cysticerci. In endemic areas, up to 25 percent of roaming pigs may be infected at any one time, and local slaughterhouses diagnose cysticercosis in 5–11 percent of pigs.[173]

Suggested Citation:"6 Epilepsy." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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The parasite is transmitted to humans when they eat poorly cooked meat. The cysticercus attaches to the intestinal mucosa and develops into the adult taenia, a flat worm that my be several meters long and live for up to 20 years. The distal portions of the parasite (proglotids) contain several thousand eggs, which are immediately infectious when released to the environment. In addition to environmental contamination, infected humans can contaminate other humans, directly, who then acquire cysticercosis.[174] When the larvae reach the nervous system (NCC) they can produce serious symptomatology, often manifested as epileptic fits and intracable headaches.[173]

The clinical manifestations of NCC are present in only 40 percent of individuals with proven larval invasion to the brain.[97] The symptomatology depends on the number of invading cysts and their localization in the central nervous system. A few cysts localized in the cerebral cortex may be responsible for focal neurological signs and symptoms, such as aphasia, hemiparesis, or partial seizures, whereas a single cyst placed within the ventricular system may produce increased intracranial pressure and sudden death.

EPIDEMIOLOGY

Data on the epidemiology of NCC have been elusive because of its clinical characteristics, with a wide array of manifestations; the variable period of incubation, from a few months to more than 20 years; the lack of adequate diagnostic methods; and the low reporting rates for the disease. Recently, with the advent of newer immunological techniques—notably enzyme-linked immunoelectro-transfer blot (EITB) and the wider use of brain computed tomography (CT)—a clearer picture of the distribution and extent of the disease has emerged. The prevalence of NCC has been estimated to be from 3 percent (based on autopsy studies) to 9 percent (based on immunological studies).[93,97,175]

To assess cysticercosis as a significant risk factor for epilepsy, researchers from Ecuador conducted an epidemiological study in the village of San Pablo del Lago, 80 miles north of Quito, the capital city, where T. solium taeniosis/cysticercosis had been shown to be endemic.[93] The study used the WHO Protocol for the Epidemiological Investigation of Neurological Disorders in Developing Countries. This protocol is based on a structured interview and a taskbased selective neurological examination. For the Ecuadoran study, a third step was added, which consisted of confirming the clinical diagnosis by immunological (EITB) and CT testing. The CT criteria for the diagnosis of NCC were based on the extensive descriptions of the condition in the literature. A symptom-free control sample population was studied to assess the statistical significance of the presence or absence of T. solium NCC for the etiology of cases presenting with seizure disorders. This approach strengthened the specificity of the protocol for the detection of T. solium infection.[93]

Suggested Citation:"6 Epilepsy." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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Complete information was collected for 2,723 individuals living in the urban nucleus of San Pablo del Lago. Thirty-one individuals were confirmed to suffer from active epilepsy, as defined in previous community-based studies. Thus, the point prevalence ratio was 1.4/1000 (confidence interval [C.I.] 7.7–15.4).

In the general group of patients confirmed with epilepsy, 16 (51.6 percent) were classified as having generalized seizures and 15 (48.4 percent) as having partial seizures. In the 14 patients with positive CT findings for NCC, 5 (35.7 percent) had generalized seizures, and 9 (64.3 percent) had partial seizures.

All patients with confirmed active epilepsy were invited to undergo further examination at the clinical center in Quito for completion of ancillary investigations for epilepsy, but 5 refused CT examinations, and 3 of these refused to have blood drawn for immunological testing. In 14 of the 26 subjects (53.8 percent) with epilepsy who agreed to be examined, there was CT evidence of past or recent NCC infection. In 11 of these 26 patients, epilepsy had first started when they were above age 20. In this group of late-onset epilepsy cases, NCC was found in 7 cases (64 percent).

Three of 6 men (50 percent) and 2 of 8 females (25 percent) for whom CT findings were consistent with a diagnosis of NCC also had EITB positivity for this infection. In total, only one-third of epilepsy patients with NCC diagnosed by CT had a concomitant positive EITB (5/14, or 35.7 percent). Four of 5 individuals studied by CT and showing single or multiple viable cysts had a positive EITB (80 percent), whereas only 1 of 9 who displayed single or multiple calcifications had a positive EITB (11 percent). One other patient with epilepsy had a positive EITB with a negative CT.

In the seizure-free random sample of the population, 118 CTs were completed. Of these, 17 were positive for NCC, for a prevalence ratio of 144/1000 (CI of 85–212). In the same sample, it was possible to have serum taken for EITB in 96 cases, 10 of which were positive for cysticercal infection, for a prevalence ratio of 104/1000 (CI of 52–167).

Chi square analysis was performed to compare the epilepsy-free random sample of the population with the epilepsy cases associated with cysticercal infection proven by either of the two clinical tests used—CT scanning or EITB testing. Among the epilepsy cases, a statistically significant difference was found for the CT diagnosis of NCC OR 6.93, CI 2.7–17.5, p < 0.001), but not the EITB diagnosis (OR 2.75, CI 0.8–7.1, p < 0.12, NS), using Mantel-Haenzel statistics. This discrepancy between the CT and EITB results may be explained on the basis of a long-standing chronic condition, in which early antibody disappearance occurs.

The results of this study indicate that the prevalence of NCC in communities in which this infection is endemic may be as high as 14 percent, when CT scanning is used as the diagnostic standard. The results also confirm that NCC is a major risk factor for epilepsy in these areas.[93] The evidence suggests that up

Suggested Citation:"6 Epilepsy." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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to two-thirds of late-onset epilepsy cases may be due to this infection in such endemic regions.

It is possible to confirm the high prevalence figures for epilepsy reported in developing countries using the WHO protocol. If the epilepsy ratio found in the Ecuadoran study is corrected by eliminating those cases linked to cysticercal infection, the remaining figure (17 patients, or 6.2/1000) is almost identical to that reported for Rochester, Minnesota (6 per 1,000).

PREVENTION

T. solium taeniosis/cysticercosis can be prevented by a long-term approach involving appropriate legislation, health education, modernization of pig husbandry practices, improved meat inspection, provision of adequate sanitary facilities, and measures to detect and treat human tapeworm carriers. However, modernization of sanitary infrastructure is expensive and beyond the current capabilities of most rural populations. Moreover, changing attitudes, beliefs, and behaviors is a difficult task that can be accomplished only after years of community health education.[162] Given political and economic realities in countries where NCC is endemic, there is little hope that all these measures can be implemented in the near future. To achieve more rapid progress in reducing active transmission of the disease, community-based interventions for the detection and mass treatment of endemic foci with taenicidal drugs have been proposed and implemented successfully in Ecuador and Mexico.[ 176] Progress in control can be attained by integrating these activities within primary health care systems. T. solium taeniosis/cysticercosis is, therefore, a potentially eradicable condition, although the concerted political action of involved governments will be needed to achieve this goal.[98,176,177]

TREATMENT

Fifteen years ago, treatment of patients with NCC was confined to excision of surgically accessible cysts and the use of steroids for the treatment of parasitic-induced inflammation. In recent years, the development of safe and effective chemotherapeutic agents has changed the prognosis for this condition.[97,98] Praziquantel and albendazole, given orally, have proven to be active against intracerebral cysts. Praziquantel is used in doses of 50 mg/kg/day, divided into three intakes, for 15 days.[178] Albendazole is usually given in doses of 800 mg/day for 8 days.[ 179,180] Higher daily dosages and longer treatment periods are sometimes needed for severe cases, or when the cysts are located within the ventricular system. Oral or intravenous steroids are now widely used, in various therapeutic schemes, to counteract the inflammatory reactions associated with both the presence of the parasite and the therapy itself. Anticonvulsants are indicated when seizures are the main manifestation of the disease. In-

Suggested Citation:"6 Epilepsy." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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testinal taeniosis is usually cured with a single dose of praziquantel, as low as 5 mg/kg [176].

Patients with parenchymal NCC typically present with seizures. In the Ecuadoran study, two of three patients with epilepsy secondary to NCC presented with partial seizures. Although anticonvulsants are routinely prescribed, Latin American researchers advocate the concomitant use of antiparasitic drugs and steroids where there is evidence of active NCC [179,180 and 181]. In fact, there appears to be a decrease in seizure frequency in patients thus treated [182,183].

The Ecuadoran study and others in Africa and Asia [90,94,184,185] revealed that individuals suffering from the consequences of NCC are subject to limiting illnesses such as intractable headaches and seizures that hamper their well-being and limit their productivity as active community members. NCC is a preventable and treatable infection. Programs and research designed to eradicate NCC in developing countries would lead to the elimination of a sizable number of epilepsy cases and the associated human suffering.

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×

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Suggested Citation:"6 Epilepsy." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
×

Summary of Findings:

Schizophrenia in Developing Countries

  • The average lifetime risk of schizophrenia is about 1 percent. Compared to its incidence and prevalence, the social and economic costs of schizophrenia are disproportionately high. The condition causes greater chronic disability than any other mental disorder, in part because of its early age of onset and the stigma of “insanity.”

  • In both developed and developing countries, schizophrenia is associated with excess mortality from a variety of causes associated with poor self-care, inadequate nutrition, heavy smoking, and medical neglect. At least part of this excess mortality is preventable.

  • A high proportion of better outcomes for schizophrenia in developing countries has been reported by numerous investigators. The reasons for this are unknown, but may involve interactions between specific genetic and environmental factors. Research on this topic could have fundamental implications for the management and treatment of schizophrenia in both developing and developed countries.

  • Schizophrenia and other psychotic illnesses can be controlled with a variety of treatments that offer significant returns in terms of symptom improvement, quality of life, and reintegration into the community. The choice of an antipsychotic therapeutic agent, however, must involve a balance between several potentially conflicting factors: clinical efficacy, profile and incidence of adverse effects, acceptability and likelihood of treatment adherence, and cost-effectiveness.

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Brain disorders—neurological, psychiatric, and developmental—now affect at least 250 million people in the developing world, and this number is expected to rise as life expectancy increases. Yet public and private health systems in developing countries have paid relatively little attention to brain disorders. The negative attitudes, prejudice, and stigma that often surround many of these disorders have contributed to this neglect.

Lacking proper diagnosis and treatment, millions of individual lives are lost to disability and death. Such conditions exact both personal and economic costs on families, communities, and nations. The report describes the causes and risk factors associated with brain disorders. It focuses on six representative brain disorders that are prevalent in developing countries: developmental disabilities, epilepsy, schizophrenia, bipolar disorder, depression, and stroke.

The report makes detailed recommendations of ways to reduce the toll exacted by these six disorders. In broader strokes, the report also proposes six major strategies toward reducing the overall burden of brain disorders in the developing world.

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