Handbook of Clinical Neurology, Vol. 121 (3rd series) Neurologic Aspects of Systemic Disease Part III Jose Biller and Jose M. Ferro, Editors © 2014 Elsevier B.V. All rights reserved

Chapter 114

Neurology in the developing world 1 2

B.S. SINGHAL1* AND SATISH V. KHADILKAR2 Department of Neurology, Bombay Hospital Institute of Medical Sciences, Mumbai, India

Department of Neurology, Grant Medical College and Sir J. J. Group of Hospitals and Bombay Hospital Institute of Medical Sciences, Mumbai, India

INTRODUCTION The worldwide global burden of disease due to neurologic illnesses, estimated at 4.2% in 1995 (Murray and Lopez, 1996), is expected to increase in the coming years. These illnesses have, until recently, received less attention in developing countries (defined as countries with low and middle income having 2008 Gross National Income (GNI) per capita below US$11 905) (Source: Country Classification World Bank, 2010) because they were considered chronic, not amenable to treatment, and too expensive to manage. We are now beginning to understand the major social and economic impact of these illnesses in the developing world. The publication Atlas: Country Resources for Neurological Disorders 2004 is a rich source of information on neurologic services in different regions of the world including the developing world. It shows the gross disparity in the neurologic care between the developed and the developing nations. Delivery of neurologic care in developing countries varies depending on the needs and resources of the country and the availability of medical and paramedical personnel. Currently there is a gross mismatch between the burden of neurologic disorders and the availability of resources including health professionals. In several developing countries, there are only a handful of neurologists serving large populations. In some countries like Bhutan there is no neurologist (Duncan, 2007). To compound the problem, neurologists tend to settle in metropolitan areas, while the rural majority remains underserved. With the increase in life expectancy, we expect a significant rise in the burden of noncommunicable neurologic disorders such as Alzheimer’s disease, Parkinson’s disease, and strokes in the developing countries. This will add to the already existing burden of

infectious diseases and nutritional disorders. Cultural practices, superstitious beliefs, and social stigma attached to diseases such as epilepsy deprive a large section of the population in these countries of available treatments, resulting in a large treatment gap (Meinardi et al., 2001). In several developing countries, medical expenses are borne by the patient and family members. Medical insurance and government support are usually lacking. The financial burden is heavy and includes direct costs of outpatient consultation, investigations, inpatient care, medications and transport (patients from rural areas often have to travel long distances to urban health care centers). The indirect cost includes the loss of earnings due to unemployment during illness and convalescence. In the large majority of these countries, there are no disability benefits. Although recent years have witnessed major advances in the management of neurologic disorders, these have not reached the majority of patients in the developing regions, due to factors such as financial constraints and a paucity of neurologists. Developing countries face a wide variation in the organization of neurologic services, education, and training and in the prevalence and presentations of neurologic illnesses. The World Health Organization (WHO) publication Neurological Disorders: Public Health Challenges has addressed several of these issues in the developing countries (Neurological Disorders, 2006).

HEALTHCARE SYSTEMS IN THE DEVELOPING WORLD AND THEIR IMPACT ON NEUROLOGIC CARE Each nation in the developing world has a different combination of public and private provision of neurologic care depending on its healthcare system. Consequently, the standards of care vary considerably at the primary,

*Correspondence to: Dr. B.S. Singhal, 131 MRC, Bombay Hospital Institute of Medical Sciences, 12 New Marine Lines, Mumbai 400 020, India. Tel: þ91-022-2206-8787/98-2104-6214, E-mail: [email protected]

1774 B.S. SINGHAL AND S.V. KHADILKAR secondary, and tertiary levels. The concept that neuroTertiary care logic care can be provided, at least in part, at the primary Tertiary neurologic care provides advanced managecare level was an important shift in healthcare planning. ment and rehabilitation for neurologic illnesses, adopts a multidisciplinary approach, and attempts to provide emerging new therapies. This specialized form of care Primary care is usually provided by teaching hospitals and some other Developing countries have, by and large, accepted the well equipped hospitals. These institutions serve as trainstrategy evolved for primary health care by the Almaing and research centers. They require adequate staff Ata Declaration (1978). It aims to provide health for and equipment. Sufficient funds are needed to provide all by its easy accessibility, cultural acceptability and the desired quality of tertiary care. Regrettably, in sevreduced cost. Due to the shortage of doctors in the develeral developing countries, only a few centers receive adeoping countries, primary health care training is also quate financial support. In recent years, the private imparted to nurses and community health workers. corporate sector has taken the initiative to provide addiSeveral developing countries have integrated this contional tertiary care centers in some countries. cept into their healthcare system. For example after Guinea-Bissau gained independence from Portugal, its government introduced a nationwide primary health HUMAN RESOURCES, TRAINING, care system (de Jong, 1996). Training was imparted to AND EDUCATION staff members (mainly nurses) at health centers, some Developing countries suffer from an inadequate number of whom then trained and supervised volunteer village of trained neurologists. Often, it is left to the general health workers. The nurses received quarterly superviphysician to provide neurologic care. The number of sion, with emphasis on case management and the use neurologists per 100 000 population differs significantly of medications. Ultimately this training improved the in developing and developed nations, ranging from 0.03 ability of health workers to diagnose epilepsy and other in Africa and 0.07 in South East Asia to 4.84 in Europe common conditions. Continuing supervision of health (Atlas, 2004). There is also a major shortage of trained workers by nurses and physicians from secondary mednurses, paramedical staff, and rehabilitation services ical centers was an essential component for the success in the developing countries. All this results in a huge burof this program (de Jong, 1996). Similar initiatives have den of work for the neurologists, who find it difficult to been undertaken by several other developing countries devote sufficient time to each patient. In the absence of The community health workers and “barefoot doctors” adequate support staff, the neurologist has also to perof China have proved to be a great help in providing priform the duties of the specialist nurse and social worker. mary health care. Moreover, because they work in the It is not unusual for neurologists to be on call 24 hours a community, primary care teams are easily able to recogday for attending to emergencies. Not much time is left nize factors such as social stigma, family problems, and for collecting epidemiologic data or doing clinical cultural factors that affect neurologic treatment. research (Khadilkar and Wagh, 2007). The schedule and structure of neurology training programs vary from one country to another. For example, Secondary care there are no formal neurologic postgraduate training Secondary care is provided by district or regional hospiprograms available in several Arab countries. Overall, tals that offer outpatient consultation and inpatient serthere are 24 residency programs (ranging from one in vices including emergency care. The staff at the Morocco to 12 in Egypt) and 162 neurology residents secondary health centers includes neurologists, inter(ranging from seven in Morocco to 120 in Egypt). In connists, residents, nurses, and trained technicians. Laboratrast, there are 133 neurology residency programs and tory facilities, electrophysiology, and computerized 1428 residents in North America (Benamer and Shakir, tomography (CT) scans are usually available at these 2009). India has, at present, 38 postgraduate neurology centers. Secondary care centers also provide technical training centers with 84 candidates taking the examinaand administrative support to primary care clinics in tion each year. In several countries, a diploma or degree their district or region. In some countries, such as India, is awarded to certify the training in neurology. However, mobile care teams from the district hospitals provide continuing education programs and the system of support to the primary care centers for common neuroaccreditation are still lacking. The available training prologic problems such as epilepsy (Gourie-Devi, 2008). grams for nursing and rehabilitation are also scarce. To Similarly, neuro-caravans of Senegal are effectively improve neurologic services, regional neurologic associreaching out to its rural communities (Aarli et al., 2007). ations and societies have been established in several

NEUROLOGY IN THE DEVELOPING WORLD countries. These societies hold conventions and seminars to improve standards of neurologic care in their respective countries. Many of them have joined the World Federation of Neurology (WFN) to meet the overall goal of improving human health worldwide by promoting prevention and care of neurologic disorders. During the WFN meetings, (earlier held once in 4 years and now to be held once in 2 years from 2011) neurologists from all regions gather to enhance their knowledge and share important data and experiences. The WFN conference held in Delhi (India) in 1989 served the cause of promoting neurology in India. It is hoped that the continuing efforts of the WFN will similarly raise the standard of neurologic care in the developing regions of Africa. The WFN education committee is promoting neurology education by initiating programs like the neurology training program in Honduras (Medina et al., 2007) which serves as a model for other developing nations. In addition, WFN has also offered a continuing medical education program to 43 countries with limited resources. This program has succeeded in improving the neurologic skills of the participants. To deal with the complexities of neurologic disorders and the recent advances in various fields of neurology, several international and national subspeciality groups have been established, such as the World Stroke Organization, the International League Against Epilepsy, and the Movement Disorder Society. So far, there are few or no subspecialists in most developing countries. Pediatric neurology still has to take root in several of these countries. Only a handful of pediatric neurologists are available for the large pediatric population of India. In most of these countries, the neurologic problems of children are handled by the few adult neurologists or by general pediatricians. Besides adequate human resources, another important aspect of neurologic care is the availability of tools and equipment to facilitate diagnosis. Recent years have witnessed major advances in laboratory techniques and imaging procedures such as CT and magnetic resonance imaging (MRI) scans. These tools require expertise and funds, both of which are scarce in the developing regions. For optimal inpatient care of patients with neurologic disorders, it is important to have an adequate number of hospital beds with trained nurses and designated wards or units. Such an organized system is usually lacking in the developing countries where patients are managed on beds allocated to internal medicine (Atlas, 2004). Shortages of beds mean that on occasion patients have to be looked after on “floor beds.” Neurologic emergencies are managed in general intensive care units by residents and nurses who have limited knowledge of neurology. Despite the availability of scientific medicine (often considered as “Western medicine”), patients in several

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developing countries seek help from practitioners of indigenous medicine and homeopathy. This can be attributed to cultural beliefs, nonavailability of cures for neurodegenerative conditions such as motor neuron disease, and pseudo claims of cure by practitioners of unproven alternative medicine. The high cost and, at times, the nonavailability of essential drugs cause patients to seek help from such healers. Unfortunately, at this time there are few governmental regulations for such practitioners in the majority of developing countries.

COMMON NEUROLOGIC DISEASES IN THE DEVELOPING WORLD The frequency and presentation of common neurologic illnesses vary significantly in the diverse regions of the developing world. These differences arise from differences in ethnic background, geographic location, cultural practices, and lifestyle. Although small epidemiologic studies have been attempted in some developing countries, the information is largely derived from hospital-based data which have their limitations. Infections, stroke, head trauma, and epilepsy account for a large share of common illnesses seen in the developing world.

Epilepsy Epilepsy is a major public health concern, affecting an estimated 50 million people worldwide. Of these, nearly 80% live in the developing countries. The WHO’s Atlas: Epilepsy Care in the World describes the global dimensions of the medical, sociological, psychological, and financial consequences of epilepsy (Atlas, 2005). Developing countries are maximally affected by these consequences. Several studies have reported that a large proportion of patients with epilepsy in these countries never receive appropriate treatment. A recent systematic analysis of the magnitude of the treatment gap in resource-poor countries found an overall rate of 56% (Mbuba et al., 2008). The main causes of this large treatment gap include high cost of treatment, nonavailability of antiepileptic drugs (AEDs), and faith in traditional treatments, superstitions, and cultural beliefs. A significant number of patients, although diagnosed and initiated on treatment, soon discontinue drugs, due to their inability to afford the treatment and ignorance of the effects of discontinuation. A study from India reported that 43% discontinued their treatment after 1 year (Das et al., 2007). The social stigma attached to this condition creates further difficulties in its management. The quality of life of patients with epilepsy is affected by the prejudices prevalent in society. Epileptic children often find it difficult to be accepted in schools.

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Finding suitable employment and arranging marriages (especially for women) also become major issues. Although precise epidemiologic data from developing countries are not available, the prevalence of epilepsy is believed to be higher as compared to the developed nations. There are wide variations in prevalence rates in different geographic regions and even within these regions. In developed countries, the lifetime prevalence rate for epilepsy ranged from 3.5 to 10.7 per 1000 personyears (Forsgren et al., 2005). In developing countries, the lifetime prevalence rates for active epilepsy varied from 1.5 to 14 per 1000 person-years in Asia (Mac et al., 2007), from 5.1 to 57.0 per 1000 person-years in Latin America (Burneo et al., 2005), and from 5.2 to 74.4 per 1000 person-years in sub-Saharan Africa (Preux and DruetCabanac, 2005). The increased occurrence of birth trauma, head injuries, infections such as tuberculous meningitis, viral encephalitis, and infestations such as neurocysticercosis is responsible for the higher prevalence of epilepsy in the developing world. Most people with epilepsy in the developing countries are diagnosed and treated by primary and secondary care physicians with no specific training or expertise in epilepsy management. The electroencephalogram (EEG) serves as a useful tool to define the type of epilepsy and the epileptic syndrome and has become available in several developing countries. However, most EEG laboratories in resource-poor countries are managed by laboratory technicians and paramedical personnel with no formal training in recording and interpreting EEGs. Consequently, EEG results are frequently misinterpreted, leading at times to overdiagnosis of epilepsy and unnecessarily prolonged AED therapy. Patients with adultonset focal seizures or unsatisfactory seizure control require brain MRI, which is either not available or not performed as per the appropriate imaging protocol. Several new AEDs have recently become available for the management of epilepsy. They are considered safer with fewer drug interactions. However, these newer agents are expensive and beyond the reach of many patients in developing countries. Nearly 25% of patients with epilepsy have refractory seizures. They need to be managed in comprehensive epilepsy centers which are scarce. Adequate facilities for epilepsy surgery in select cases are also not available in the majority of these countries. The regional epilepsy associations, in close collaboration with international organizations for epilepsy and the WHO are doing their best to improve the quality of epilepsy care in these regions.

Headache Headache disorders affect 15–20% of the general population. Although few population-based prevalence

studies of headache are available in the developing countries, it is believed to be as prevalent as elsewhere in the world. Primary care physicians are usually the first to be consulted. Therefore it is necessary for them to effectively diagnose and treat primary causes of headaches such as migraine, tension headache, and medication overuse headache. They should also be able to exclude uncommon but serious causes of secondary headaches such as meningitis, subarachnoid hemorrhage and intracranial space-occupying lesions and expeditiously refer them to secondary or tertiary centers. There can be regional variations of the trigger factors for common tension headache or migraine. Stress levels may vary depending on cultural and socioeconomic background. In India, the habit of not having breakfast and observing frequent fasts are listed as common triggers for migraine (Ravishankar, 2004). Triptans and other migraine medications have proved beneficial, but are infrequently used due to their high costs and nonavailability in many regions. Realizing the importance of headache as an important cause of disability, the WHO launched the “Lifting the Burden” campaign in March 2004 in a formal partnership with international nongovernmental organizations such as the World Headache Alliance, the International Headache Society, and the European Headache Federation (Steiner, 2004).

Central nervous system infections Despite the availability of effective antibiotics and vaccines, infectious diseases still result in high mortality, severe disability, and a heavy economic burden for individuals, families, and health systems in the developing countries. As a region, Africa is characterized by the greatest infectious disease burden and, overall, the weakest public health infrastructure among all the developing regions in the world (Davis and Lederberg, 2001). Tuberculosis, malaria, and acquired immunodeficiency syndrome (AIDS) are the leading causes of death. Some diseases such as poliomyelitis, leprosy, and syphilis have virtually disappeared in the developed world, but are still endemic in the developing regions. Overcrowding, poor resources, and lack of effective disease control programs result in a high prevalence of infectious diseases. AIDS accounts for high mortality in the developing regions with sub-Saharan Africa being most affected. Nearly 70% of all HIV-infected patients and 90% of all cases of maternal–fetal transmission are seen in the sub-Saharan region (Towards Universal Access, 2008). Neurologic complications occur in nearly 39–70% of patients with AIDS. Tuberculosis, toxoplasmosis, cryptococcal meningitis, and cytomegalovirus encephalitis are the common opportunistic infections seen in AIDS patients. Lack of resources and financial constraints

NEUROLOGY IN THE DEVELOPING WORLD make it difficult to care for these patients. Awareness of the illness, use of preventive measures such as condoms and affordable antiretroviral treatment would go a long way in mitigating the suffering of these patients. Viral encephalitis due to known and unknown viruses is frequently seen in the developing regions. The type of infection often depends on the geographic location. Japanese B encephalitis is a leading cause of encephalitis in Asia and results in high mortality and morbidity, especially in children. Equine viral encephalitis is common in Colombia and Venezuela (Watts and Oberste, 2000). An outbreak of encephalitis due to Nipah virus was described in pig farm workers in Malaysia (Chua et al., 1999). Subacute sclerosing panencephalitis, rarely seen in the West, continues to be prevalent in children of South Asia and the Middle East where measles immunization is still not universal. Through the Global Polio Eradication Initiative program of the WHO (2003), most countries had been declared free of poliomyelitis by 2008, except for Afghanistan, India, Nigeria, and Pakistan (Global Polio Eradication Initiative, 2008). Regrettably, several lives are still lost every year due to rabies in Asia and Africa, which occurs largely due to the bite of nonvaccinated rabid stray dogs. Outbreaks of acute hemorrhagic conjunctivitis with occasional neurologic complications caused by EV70 virus and other enteroviruses have occurred intermittently in Asia (Wadia et al., 1983). Among the mycobacterial diseases, neurologic complications of tuberculosis (TB) account for high mortality and morbidity in the developing world. In 2008, there were an estimated 8.9–9.9 million incident cases of TB (7.4 million in Asia and sub-Saharan Africa), 9.6–13.3 million prevalent cases, 1.1–1.7 million deaths from TB among HIV-negative people and an additional 0.45– 0.62 million TB deaths among HIV-positive people (Global Tuberculosis Control, 2009). Often the diagnosis is delayed, resulting in high rates of complications such as hydrocephalus, strokes, cranial nerve palsies, and paraparesis. HIV infection and multidrug resistance have made TB a more complex and deadly disease. Bacterial meningitis continues to be an important cause of mortality and morbidity, especially below the age of 15 years. Streptococcus pneumoniae and Neisseria meningitidis are responsible for 80% of cases (van de Beek et al., 2006). The highest incidence of meningococcal meningitis is found in sub-Saharan Africa – known as the meningitis belt. This region extends from Senegal in the west to Ethiopia in the east (Gessner et al., 2010). Leprosy is still is a major health issue in the developing regions of Asia, Africa, and South America. It must be remembered as an important cause of mononeuritis multiplex and symmetric, predominantly sensory polyneuropathy, even in the absence of obvious skin lesions.

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The diagnosis of this treatable condition is often delayed because of late presentation due to associated social stigma. Malaria is responsible for the death of at least 1 million people every year, 90% of whom live in sub-Saharan Africa. The highest death toll occurs in children under 5 years of age (World Malaria Report, 2008). Despite available prevention and treatment, the burden of malaria remains high. In the developing world there is a tendency to empirically treat all fevers with antimalarials. In the rural areas, there is also large-scale underdiagnosis of malaria because many patients do not seek or are unable to reach healthcare. Of the various forms of malaria, cerebral malaria caused by Plasmodium falciparum takes the highest toll of life. The philanthropic Bill and Melinda Gates Foundation has taken an active interest in reducing malaria-associated morbidity and mortality. Cysticercosis is a major health problem, especially in Africa, Asia, and Latin America. The eggs of Taenia solium contaminate the soil. Human beings acquire cysticercosis through contaminated food items. Therefore vegetarians and others who do not eat pork also acquire cysticercosis. Neurocysticercosis is a frequent cause of epilepsy (Medina et al., 1990; Rajshekhar et al., 2003). It may also present with headache, transient stroke-like symptoms, cognitive decline, and even hydrocephalus. The lack of basic sanitary facilities is one of the important causes for its high prevalence in these regions. The WHO has emphasized that all endemic countries should adopt policies and strategies for the control of taeniasis and cysticercosis. Other conditions largely seen in sub-Saharan Africa include sleeping sickness (African trypanosomiasis) caused by the protozoan parasite Trypanosoma, through the bite of tsetse flies, and cerebral schistosomiasis, caused by Schistosoma japonicum. Cerebral schistosomiasis may present with seizures, headache, or spinal cord dysfunction. Today, with frequent overseas travel and migration, physicians in the developed nations need to be alert to the possibility of such illnesses occurring in their regions.

Stroke Stroke is one of the leading causes of mortality and morbidity in the world. There is a paucity of accurate stroke prevalence data in the developing regions. According to WHO estimates, death from stroke in the low and middle income countries accounted for 85.5% of stroke deaths worldwide in 2005 (Strong et al., 2007). With the increase in life expectancy, urbanization, and changes in lifestyle, the burden of stokes in the developing countries will continue to rise in the coming years. By 2020, it is estimated

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that 19 out of 25 million annual stroke deaths will be in developing countries (Lemogoum et al., 2005). There are regional and intraregional variations in the prevalence, severity and type of stroke in different developing countries. A review of stroke epidemiology in Latin America and the Caribbean revealed a higher stroke mortality in these regions than in developed countries. Diabetes and hypertension were the major risk factors (Lavados et al., 2007). In China, the total ageadjusted incidence of stroke was similar to that of developed countries. The age-adjusted stroke prevalence has varied from 260 to 719 per 100 000 in different regions of China (Liu et al., 2007). The prevalence of stroke was higher in the urban areas than in rural areas. The prevalence of hemorrhagic strokes was higher than in the West, with the figure reaching as high as 55.4% in the city of Changsha in China (Yang et al., 2004). Similarly, the occurrence of intracranial atherosclerosis was high in China (Wong et al., 2007). Hypertension was reported to be the most important risk factor for stroke in China. Of other Asian regions, the prevalence of stroke has varied from 90–222 per 100 000 in India to 690 per 100 000 in Thailand (Poungvarin, 1998). In Africa, although the overall stroke prevalence was lower than in high-income countries, the prevalence of severe and disabling strokes was much higher. The agestandardized mortality and case fatality for stroke were also higher than in the developed world (Mensah, 2008). Besides, the mean age of stroke patients in sub-Saharan Africa was lower, at 58 years, which is about 10–15 years younger than patients in developed countries (Bonita and Truelsen, 2003). Cerebral hemorrhage was the leading cause of fatal stroke in sub-Saharan Africa (Connor et al., 2007). Hypertension was the most significant risk factor in this region. Among Arab countries, the annual stroke incidence ranged from 27.5 to 63 per 100 000 and prevalence was between 42 and 68 per 100 000 population. Ischemic stroke was the commonest subtype in all series except Sudan where intracerebral hemorrhage accounted for 41% of strokes. Hypertension, diabetes mellitus, hyperlipidemia, and cardiac disease were the commonest risk factors (Benamer and Grosset, 2009). Other risk factors in the developing regions include infections such as CNS tuberculosis and syphilis, rheumatic valvular heart disease, and cerebral venous thrombosis. Stroke management in the West has benefitted greatly by the establishment of dedicated stroke units and the availability of special treatment procedures such as thrombolysis, stenting, and endarterectomy. These facilities are only available in very few centers in some developing countries. The majority of them do not have, as yet, any access to the above procedures. Patients in rural areas are deprived of basic stroke care due to shortage of trained medical personnel and nonavailability of

CT scan. At present, the emphasis has to be on increasing public awareness and focusing on preventable risk factors such as hypertension, smoking, diabetes, and hyperlipidemia to reduce the burden of stroke in the developing world. The Global Stroke Initiative, a collaborative effort between the WHO, the International Stroke Society, and the WFN and the efforts of the national stroke organizations will go a long way in the prevention and management of stroke in these countries.

Alzheimer’s disease Alzheimer’s disease and vascular dementia are the leading causes of dementia in the world. An expert group, working for Alzheimer’s Disease International, estimated that 24.2 million people are affected by dementia worldwide (Ferri et al., 2005). Of these, nearly 60% live in the low and middle income countries. With increase in life expectancy it is expected that the number of patients with Alzheimer’s disease will rise significantly in these countries. Well-designed epidemiologic research is lacking in developing countries. Several studies have suggested that the prevalence of dementia may be considerably lower in developing than in the developed world (Hendrie et al., 1995; Chandra et al., 1998; Prince, 2000). These data may reflect underdetection in the early stages and lower exposure to environmental risk factors. In India, early signs of dementia in the elderly are often attributed to a normal aging process (Chandra et al., 2006). Several treatable conditions such as nutritional deficiency (B12 deficiency), hypothyroid state, and infections such as tuberculous meningitis, or infestations such as cysticercosis should be excluded as a cause of dementia in the developing countries. HIV infection has also become an important cause of dementia especially in Africa. Caring for persons with dementia is becoming increasingly difficult in the developing world. Earlier, these persons were well looked after because of the joint family system with a large number of family members living together, especially in the rural areas. Today, migration to urban areas, nuclear families, working women, children going overseas, the “single child family” in China, and the high mortality rates of young HIV individuals in Africa have reduced the number of family members who can care for the demented persons. The behavioral and psychological symptoms of dementia significantly increase the burden of the caregivers and are the main cause for institutionalization. The cost of antidementia drugs such as the anticholinesterase inhibitors and antipsychotic drugs and expenses for inpatient care have proved beyond the reach of many in the developing regions. The 10/66 group, with links to Alzheimer’s Disease International, is carrying out population-based research into dementia and aging in low and middle

NEUROLOGY IN THE DEVELOPING WORLD income countries. The term “10/66” refers to the twothirds (66%) of people with dementia living in low and middle income countries and the 10% or less of population-based research that has been carried out in these regions (Prince et al., 2004).

Multiple sclerosis Multiple sclerosis (MS) is a common disorder, especially in the West, predominantly affecting young individuals. Over time, a significant number of these patients get disabled and wheelchair-bound. As with the other neurologic conditions discussed above, there is a lack of epidemiologic data concerning MS from developing countries, especially in Asia and Africa. The Atlas: Multiple Sclerosis Resources in the World (2008) published by the WHO and the Multiple Sclerosis International Federation (MSIF) provides useful global information on MS. The prevalence of MS has been reported to be low in the developing countries. However, with the growth of neurology and newer diagnostic procedures, especially MRI, MS is being increasingly diagnosed in these regions. Whether or not the increased numbers reflect an ongoing change in prevalence awaits epidemiologic analysis. Unlike in the past when Iran was considered a low prevalence region for MS, a recent epidemiologic study from the province of Isfahan in Iran reported the period prevalence of MS to be 35.5 per 100 000 making it a medium to high-risk region for MS (Etamadifar et al., 2006). The precise reasons for the relatively low prevalence of MS in developing countries are not known. Both genetic and environmental factors may be playing a significant role. In studies where persons have migrated from low-risk to high-risk regions, it was noted that they carried the risk of the region where they were born, emphasizing the role of environmental factors (Elian and Dean, 1987). However, in the small population of Parsis (about 70 000) who migrated from Iran and settled in India for well over 200 years, the prevalence of MS was high (21 per 100 000) as compared to the general population (Bharucha et al., 1988). We do not know if it is related to their ethnic origin or their lifestyle in India, which is akin to that of Western society. MS in the developing countries, as elsewhere, also affects the young (average age of onset around 25–30 years) and is more common in women than men. In Asia, two forms of clinical presentations have been described: (1) clinical features restricted to optic nerve and spinal cord (designated as optico spinal MS (OS MS) or Asian MS) (Kuroiwa et al., 1977); (2) manifestations involving cerebellum, brainstem, cerebral white matter, optic nerve, and spinal cord (Western MS). Although there

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are no well conducted studies, the course of MS is believed to be similar to that in the West. Neuromyelitis optica (NMO) is reported to be more frequent in Asia and Africa than in the West. It occurs both as a monophasic and a relapsing illness. These patients have longitudinally extensive myelitis (>3 vertebral segments) with normal brain MRI, or if abnormal, atypical for MS, thus satisfying the revised criteria for NMO (Wingerchuk et al., 2006). Data regarding the presence of aquaporin 4 in NMO in these countries are not available. Acute disseminated encephalomyelitis (ADEM), another CNS demyelinating disorder, is as frequent as in the West. In the past, several cases of ADEM occurred following the Semple type of antirabies vaccine. This has now significantly reduced with the introduction of human diploic cell vaccine. Intravenous methylprednisolone for the acute episode of MS and most drugs for symptomatic treatment are available in the developing regions. However, the treatment gap is large due to the limited access to neurologic services. Disease-modifying agents for MS such as b-interferons and glatiramer acetate are prohibitively expensive for most patients. Rehabilitation services are also limited. Fortunately, in several of these countries, active support groups in association with MSIF are playing an active role in increasing the awareness of MS and helping the patients and their caregivers. Although MS is a frequent cause of noncompressive myelopathy in the developing countries, several cases of myelopathy remain undiagnosed. Clusters of myeloneuropathies of unknown etiology have been reported from India, Africa, Seychelles, Caribbean islands, Jamaica and Colombia. Tropical myeloneuropathies due to B12 deficiency, other nutritional deficiencies, cyanide intoxication due to cassava consumption, and lathyriasis have been described from the developing countries (Roma´n et al., 1985). Tropical spastic paraparesis due to HTLV1 virus (HAM/TSP) as a cause of myelopathy occurs frequently in the Caribbean islands and Africa (Proietti et al., 2005). Eales’ disease, causing visual affection in young males due to periphlebitis, vascular proliferation, and retinal hemorrhage, occurs frequently in India. It is occasionally associated with an acute or subacute severe myelopathy (Singhal and Dastur, 1976).

Parkinson’s disease and movement disorders Parkinson’s disease (PD) has a worldwide occurrence, affecting 1–2% of individuals over the age of 65 years. The overall prevalence of PD has varied widely from 18 to 418 per 100 000 persons (Zhang and Roma´n, 1993). There is a paucity of epidemiologic data on PD in the developing regions. The prevalence in rural Tanzania (Africa) was 20 per 100 000 persons (Dotchin et al.,

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2008), while in China it was reported to be similar to that of developed countries (Zhang et al., 2005). In India, although the prevalence in the general population was low (16–27 per 100 000), a high prevalence of 328.3 per 100 000 was reported in the Parsi population (Bharucha et al., 1988). This difference in prevalence rates may be due to environmental risk factors or variations in genetic susceptibility. The clinical features of PD in developing countries are the same as elsewhere. Cases of early onset PD below the age of 40 years (juvenile and young onset) with a presumed genetic basis are also seen. However, many cases remain undiagnosed due to the limited number of neurologists. Drugs for the management of PD are available in most developing countries. However, not all patients can afford the cost of long-term medication. Therefore, the treatment gap in developing countries is large. Facilities for deep brain stimulation and other surgical procedures in advanced PD are currently available only in a minority of centers of some developing countries. A wide spectrum of hyperkinetic movement disorders is seen in developing regions. Due to the high prevalence of rheumatic fever in Asia and Africa, Sydenham’s chorea occurs more frequently in these regions (Karpatis and Currie, 1999). Huntington’s disease (HD), a dominantly inherited neurodegenerative disorder, has an occurrence of around 70 per million in persons of Western European descent, but only one per million people of Asian and African descent (Walker, 2007). One of the world’s highest prevalence rates is seen in the isolated population of the Lake Maracaibo region of Venezuela, where HD affects up to 7000 per million people (Avila-Giron, 1973). X-linked recessive dystonia, called Lubag’s disease, has been reported almost exclusively in male natives of Panay Island in the Philippines. The initial dystonic movements later get overshadowed by the parkinsonian features as the disease advances slowly over 10–15 years (Lee et al., 2001). Wilson’s disease (WD), an autosomal recessive genetic disorder of copper metabolism, may present with either predominantly hepatic or neurologic involvement (Das and Ray, 2006). WD patients may present with a wide range of movement disorders such as parkinsonian features, chorea, dystonia, myoclonus and tics. WD is common in countries such as India where consanguineous marriages are common (Taly et al., 2009). The Movement Disorder Society and its regional chapters are surveying the educational needs of developing countries, arranging various programs to improve the care of patients with movement disorders. It is hoped that an increased number of neurologists with special interest in movement disorders, along with community and government support, will ease the burden of movement disorder diseases.

Traumatic brain injury Traumatic brain injury (TBI) is a leading cause of death and disability throughout the world. It is especially frequent in the developing countries. The major causes of TBI include road traffic injuries (RTI), falls, and violence. In India, RTI and falls accounted for 45–60% and 20–30% of TBI respectively (Puvanachandra and Hyder, 2009). In Eastern China, 61% of TBI were due to RTI; of these, approximately one-third were motorcyclists, 31% pedestrians, while motor-vehicle passengers accounted for 14% (Wu et al., 2008). Latin American and Caribbean nations also reported a high occurrence of RTI, accounting for 66% of all TBI (Puvanachandra and Hyder, 2008). A similar pattern was observed in Africa, with Nigeria recording a high RTI figure of 80% of all TBI (El-Gindi et al., 2001). Several reasons account for the large number of road traffic accidents in developing countries. These include a relatively high number of vehicles combined with inadequate number and poor condition of roads, careless driving, and disregard of safety regulations such as wearing of helmets and safety belts. Driving while facing oncoming traffic, reckless overtaking and wandering of stray animals on the roads also increase the risk of accidents. Stiff penalties for driving under the influence of alcohol are also not strictly enforced. RTI and falls often prove fatal at the site of the accident. Life is also lost during transportation. Services for immediate assistance and quick transportation to medical centers are not well developed in the majority of developing countries. The availability of trained paramedics is scarce; ambulance drivers and attendants often lack the requisite training and skills to provide optimum care during transportation. Although some specialized trauma care centers and neurosurgical services have become available in some developing countries, they are grossly insufficient to meet the needs of the population. In order to decrease the burden of TBI in developing countries, there is an urgent need to improve infrastructure, provide better roads, develop highquality trauma care centers, and strictly enforce safety regulations.

CONCLUSION Nearly all neurologic illnesses occurring in developed countries are also seen in the developing world, but with varied frequency and clinical presentations. The high prevalence of neurotuberculosis, HIV-AIDS, malaria, and TBI significantly contribute to the disease burden in the developing world. The incidence of noncommunicable diseases including Alzheimer’s disease, Parkinson’s disease, and stroke is expected to increase due to increasing life expectancy, urbanization, and changing lifestyle.

NEUROLOGY IN THE DEVELOPING WORLD It is therefore imperative that nations in the developing world strive hard to streamline and optimize their healthcare delivery systems to meet these challenges. Strategies should be in place to improve the health infrastructure, provide an adequate number of trained medical personnel, and make available essential drugs and procedures at affordable prices to all patients with neurologic disorders. Rehabilitation services, which are largely scarce, need to be greatly improved in these countries. With the incorporation of information technology and telemedicine, it should be possible to provide medical services even in the remote areas of the developing countries. In recent times, the international and regional neurologic organizations are actively promoting the cause of neurology in the developing countries. While progress has been made particularly in the last decade, more efforts are rapidly needed to improve neurologic care in the developing world. The beginnings have been made but a large distance still needs to be covered.

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