Epilepsy: treatment in low and middle income countries …

Epilepsy & Seizures

Updated 04.08.2024
Released 10.14.2009
Expires For CME 04.08.2027

Epilepsy: treatment in low and middle income countries

Authors: Karla Mora Rodriguez, Selim R Benbadis MD

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Editor: John M Stern MD

Epilepsy: treatment in low and middle income countries

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Introduction

Overview

About 80% of people with epilepsy live in low- and middle-income countries (43; 66). Studies have shown that up to 70% of newly diagnosed children and adults with epilepsy can be successfully treated with antiseizure medications (27). In lower income regions, up to 75% of people with epilepsy may not receive the treatment they need (13). Earlier and more recent studies have reported a theoretical improvement in the epilepsy treatment gap, though this is still unproven (16; 56).

Historical note. The earliest trace of a seizure portrayal goes back to an inscription in a 4000-year-old tablet found in Mesopotamia (30). About 2000 years later, the Babylonians wrote the Sakikku, a medical text that provides a detailed report of distinct types of seizures and their characteristic presentations, with terms such as miqtu (fall), hayyatu (fit), and sibtu (seizure) and a description of the postictal state. They were also able to recognize prognostic features, though evil spirits were tied to causation, and spiritual interventions were thought to be the treatment (23). Since that time, humanity has linked epilepsy to supernatural events, and even now, a deeply rooted negative social influence prevails around the world.

Later, the Egyptians (circa 1700 BC), the Chinese (770–221 BC), and the school of Hippocrates (around the fifth century BC) challenged the supernatural basis of epilepsy and hypothesized that the brain was the source of this disorder (70; 23). By the seventeenth and eighteenth centuries, the Hippocratic concept of epilepsy as a brain disorder began to resurface (23). Among the many distinct diagnoses confused with epilepsy, the most frequent ones were hysteria, tetanus, tremors, rigors, and other paroxysmal movement disorders. During these two centuries, health entities such as the World Health Organization (WHO) and the International League Against Epilepsy (ILAE) made efforts to separate “nervous disorders” from “mental disorders,” which led to the beginning of modern neurology in the nineteenth century.

An understanding of the basis of epilepsy among individuals without formalized education has been an issue. Consequently, a considerable number of people residing in low- and middle-income countries believe that the cause of seizures and epilepsy is supernatural (demonic possession, witchcraft, and the divine). Additionally, mental illness is also confused as being part of the disease (59). A growing number of pharmacological treatments have become available year after year at a reasonable price all over the world, including in low- and middle-income countries. However, archaic ideas on the etiology of seizures and epilepsy create a predicament when attempting to ensure treatment initiation and compliance.

Key points

	• The gap in epilepsy treatment between low-, middle- and high-income countries is a well-known reality.
	• The first step in correcting the disparity in the treatment of epilepsy is to identify the precise etiology of the problem.
	• Treatment guidelines, as well as applicable health policies, are crucial in the appropriate management of epilepsy in low- and middle- income countries.
	• The utilization of newer, advanced technologies could be paramount in teaching, preventing, and treating epilepsy.

Magnitude of the burden

Close to 80% of people with epilepsy live in low- and middle-income countries (70). The average incidence of epilepsy in low- and middle-income countries is 61 per 100,000 person-years, compared to 45 per 100,000 person-years in high-income countries (14; 13). In South Africa, the incidence was found to be as high as 180 to 250 per 100,000 people (13). The lifetime prevalence was 7.6 per 1000 people in low- and middle-income countries, and up to 15 per 1000 people in rural areas, compared to 5 per 1000 people in high-income countries (14; 13).

Interestingly, both the incidence and prevalence of epilepsy in people with low socioeconomic status living in high-income countries is comparable to that observed in people residing in low-income countries (24). Shared risk factors, such as limited economic resources and lack of education, could explain this finding.

Patients with epilepsy in low- and middle-income countries and with low socioeconomic status in high-income countries also suffer from increased risk of premature mortality of all causes and epilepsy-related mortality (21; 10). Mortality in epilepsy is subdivided into (1) mortality directly attributed to epilepsy (27%), which includes status epilepticus and sudden death in epilepsy (SUDEP) syndrome, and (2) indirect causes of death, such as drowning, burns, head injury, and falls (20%) (21). Overall death rates in people with epilepsy in low- and middle-income countries are 2.6 times higher than in the general population in those same countries (35). Mortality is also higher in people with chronic epilepsy, especially among the young (21).

Factors that contribute to incidence rates in low- and middle-income countries are parasitic diseases (neurocysticercosis, plasmodium falciparum infection, schistosomiasis, onchocerciasis, toxocariasis, and paragonimiasis), HIV/AIDS, trauma, perinatal morbidity, and consanguinity (13).

Studies in these territories have suggested that the prevalence of epilepsy in low- and middle-income countries is uniform at 4 to 10 per 1000 (21). Sub-Saharan Africa and Central and South America reported the highest prevalences of epilepsy. Multiple variables could explain these findings, such as lower reporting rates, lack of age adjustment, methodological differences between studies, increased risk factors, diagnostic and classification limitations, and rural versus urban environments, among others (48; 40).

Etiological factors

The results of research directly modify the development of local guidelines for the prevention and management of epilepsy, the investment in education of primary healthcare workers and community physicians, and the support for further clinical research.

A definite etiology of epilepsy is not found in around 40% to 50% of patients (70; 55; 09). When known, etiology is divided into structural, genetic, metabolic, infectious, or immune categories. Of these, broad etiologic subcategories are perinatal (trauma, asphyxia/hypoxia, ischemia), brain malformations, traumatic brain injury, ischemic or hemorrhagic stroke, CNS infections, neoplasia, and genetic syndromes (70; 24; 53). Most of these could represent modifiable risk factors.

Some studies have shown that parasitic (Taenia solium–neurocysticercosis) infections of the CNS or antibodies towards them, the incidence of HIV/AIDS and other transmissible diseases, consanguinity, low cognitive reserve (dictated by low socioeconomic status), and perinatal risk factors could be factors that explain the higher incidence of epilepsy in low- and middle-income countries and in the low-income population in high-income countries (24; 26; 58; 57).

Multidisciplinary approaches that could potentially reduce the incidence of epilepsy (especially in low- and middle-income countries) are adequate perinatal care, exposure reduction, treatment and eradication of parasitic, viral, and bacterial infections (53; 57), immunization of communicable diseases, enforcement of traffic regulations for diminishing brain trauma, and stroke incidence reduction through vascular risk factor stratification and treatment (06; 24).

Studying the mechanisms for the resultant inflammatory pathways in the brain to develop novel therapies that could interfere with these pathways and reduce seizure risk has also been proposed (40; 57).

Diagnostic aspects

Epilepsy specialists provide care to people with epilepsy in 88.6% of high-income countries, but they are present in only 55.6% of low-income countries and are available without charge in about 67% of these low-income countries (70; 11).

According to the World Health Organization, a local policy for neurologic disorders is present in 28% of the countries, 23% have a guideline for neurologic conditions, 17% have legislation in epilepsy, with epilepsy included in the annual reporting registry in 65%, and only 4% have a budget defined for neurologic disorders (71). The median percentage of adult neurologists per 100,000 people in low-income countries is 0.03%, and it is 0.13% in middle-income countries. Of these, 95% practice in the capital city, 48% in urban areas, and 0% in rural areas, which leaves neurologic care for primary care providers in 98% of the cases. Additionally, only 23% of low-income countries have a guideline for neurologic disorders.

The median number of professionals per 100,000 population who are members of an organization of epilepsy specialists is 0.17 in South East Asia and Africa, 0.31 in the Western Pacific, 0.33 in the Eastern Mediterranean, and 0.35 in the Americas, compared to 2.15 in Europe (52). Professional organizations of epilepsy specialists do not exist in 64.6% of low-income countries, compared with 22.9% of high-income countries (42). Also, the median number of professionals per 100,000 population who are members of an organization of epilepsy specialists varies across different income groups in countries, with 0.19 in low-income countries compared to 1.83 in high-income countries (70).

Imaging

Computerized tomography (CT) scanning is available in approximately 70% of low-income countries but has only limited diagnostic capabilities (38). MRI is much more useful in the evaluation of epilepsy but is available in only 30% to 60% of low-income countries (70; 06; 38). The successful use of neuroimaging technologies is limited by the availability of physicists to program its software, technicians to control the hardware, and experienced neuroradiologists to report the studies performed. Frequently, the economic means are also insufficient for the regular maintenance and repairs of the equipment. Several studies performed evidence the gap in imaging technologies between low-income countries and high-income countries (20). The use of technological advances in the field of artificial intelligence and machine learning, as well as remote connected medical facilities with specialists, could partially aid in study production and interpretation in the absence of a local specialized crew.

Electroencephalography (EEG)

Access to EEG is scarce in many low- and middle-income countries. In many areas of these countries, even basic routine EEG is not available, and the overall availability is around 63% in low-income countries. Similarly, long-term video-EEG monitoring is available in 21.7% of low-income countries, as compared to 77.1% of high-income countries (70). The availability is often limited to high-income individuals in these countries and is relatively inaccessible to the poor (06; 38). Appropriate guidelines for the correct interpretation of the studies are also lacking in most low-income countries (06).

Ambulatory video-EEG could serve as an alternative to inpatient monitoring (05; 49). In many centers, this technology could be more widely used, and it should be the focus of management strategies in low-income countries with limited access to diagnostic testing. It offers the possibility of remote interpretation by experts in the field located outside of these underserved regions. Several companies and hospitals already provide video-EEG options with remote analysis for routine, urgent, and prolonged video-EEG monitoring (31; 07; 51). The use of volunteers and humanitarian organizations makes this approach very low cost to underserved communities, if not free of charge (61). A harmonious cooperation between healthcare providers and regulatory agencies around the world is required for the successful implementation and standardization of this approach (34; 51; 41).

New diagnostic technological aids

A myriad of medical technological advances has occurred in the last few decades. The use of selected tools may well assist in research, training, diagnosis, and treatment in epilepsy and could be particularly helpful to close the management gap between low- and middle-income countries.

An illustration of the use of technology in neurology is web applications (apps) for epilepsy diagnosis, such as the first app developed and tested in Nepal, which analyzes the likelihood ratio of epileptic events as differentiated from mimickers after asking 50 questions from a database (NetProphets Cyberworks). After comparing it to a specialist evaluation, it had a sensitivity of 88% and a specificity of 100% (46).

A study conducted in the Republic of Guinea compared a standard 21-lead EEG to a portable 14-lead cap with a Smartphone Branner-2 (SBS-2) with the capability to transmit data to a web-based platform (69). The first was administered by a U.S. board-certified EEG technologist, and the latter was administered by medical students and neurology residents after less than an hour of training. Both were read by randomly assigned North American board-certified neurologists and neurophysiologists. The study showed 43% sensitivity and 96% specificity in detecting epileptiform changes in children with epilepsy using the SBS-2 EEG when compared with standard EEG.

Many phone apps have been created to help with the task of bringing access to care to low- and middle-income countries. One such app, Epilepsy Diagnosis Aid, was developed for use by nonphysician health workers to aid in the diagnosis of epilepsy in low-income countries. The app was studied in a high-income country and in rural low-income countries and showed a high sensitivity and specificity for epilepsy. Another new app used a validated algorithm to help providers who lack experience in epilepsy management classify seizures and choose appropriate antiseizure medications for their patients with the disease (04). Numerous other apps are available to the general public for self-management of epilepsy and are in the process of refining their efficiency (01).

Telemedicine (telephone and videocalls) is increasingly being used in high-income countries and should also be promoted in low- and middle-income countries, with emphasis on providing access to specialists in rural and low-income areas (46; 69; 32). Utilization of digital databases and cloud storage is of great importance for the reporting of EEGs by specialists in the field of epilepsy (69).

In the absence of formal video monitoring units, standalone videos of seizures and seizure-like events are incredibly useful and low cost. Cell phone and tablet cameras are already informally being used in daily practice. The quality of such videos has proven to be adequate for interpretation in the clinical setting (02; 60). However, the process should be formalized and standardized. Patients and caretakers should be instructed on how to use their devices to optimize the quality of the recordings and to provide the necessary information to the clinician (15; 60).

Even more basic software can be used to improve patient care by increasing connectivity between patients and physicians as well as inter-physician communication, webpage use, email, specialized messaging systems, regular phone calls, and SMS messages (46).

Technological advancements have permitted the use of movement patterns along with the measurement of basic vital signs (heart rate, blood pressure, and pulse oximetry) in the identification of seizure burden in a patient. These wearable technologies are on the rise, and although they can currently be expensive to patients in low-income countries, they could be included in future public policies for use in selected populations. Hardware and software equipment could also be the focus of international aid donations.

Therapeutics

A consensus definition of the “treatment gap” was adopted by international experts sponsored by the ILAE: “The difference between the number of people with active epilepsy and the number whose seizures are being appropriately treated in a given population at a given point in time, expressed as a percentage” (39). The treatment gap has been shown to be 75% in low-income countries and 50% in middle-income countries (40). Notably, rural areas are more affected than urban and suburban areas. A study in India showed a treatment gap of 40% to 90% in rural areas versus 22% to 50% in suburban and urban regions (65; 13).

One of the major barriers to the appropriate treatment of epilepsy is the lack of access to medical care and antiseizure medications in both high-income and low-income countries.

The attributed causes with the highest medians have been related to the health systems: inadequately skilled personnel, lack of available drugs, and excessive cost of treatment. Improved training of health workers providing the first level of contact in case detection, initiation of treatment with antiseizure medications, follow-up, and monitoring for compliance and adverse effects might be the most cost-effective ways to decrease the global treatment gap (39).

Both cultural and socioeconomic factors can affect the treatment gap by altering health-seeking behaviors (63) and access to care. The belief that the cause of epilepsy is a supernatural event causes a deviation of care from Western medical treatment to traditional healers (68; 50; 39; 63; 23). Depending on the area of residence (urban vs. rural), the impact of cultural beliefs, and economic status, inadequate treatment could perpetuate as much as 6 to 14 years (50).

Antiseizure medications

The wide global disparity in the availability of treatment modalities is multifactorial. The inequalities may include “hardware” (eg, availability of technologies and reliable drug supply) or “software” (eg, availability of expertise and access to health care) factors. Both are often dictated by economic constraints (70).

Most countries have availability of at least one antiseizure medication, 42% have it available in the primary care setting, and it is obtainable with in-hospital care in 48%.

A list of essential medicines is updated every 2 years by the World Health Organization (72). It compiles pharmacologic agents that fit health care necessities of the world population according to the prevalence and public relevance of a disorder. The list is intended to provide affordable global prices. Based on this list, the supply of low-cost antiseizure medications, such as phenobarbital, phenytoin, carbamazepine, and valproic acid, should be possible. However, the inclusion of these drugs in local lists of essential medications is variable (19), and their costs differ widely from country to country.

Phenobarbital is included in 96%, carbamazepine in 82.6%, phenytoin in 68.2%, and valproic acid in 62.5% of the countries. The cost of carbamazepine and valproic acid in Europe and the Western Pacific is almost half that of other regions. The cost of phenobarbital is 2.7 times higher in South East Asia than in Europe (70).

Newer, more effective, and safer medications are becoming more accessible in low- and middle-income countries. Nevertheless, they are mostly available to higher income individuals in those countries (64; 44; 03).

Epilepsy surgery

The outcome of epilepsy surgery in low- and middle-income countries seems to be comparable to that of high-income countries in terms of quality of life and rates of seizure freedom, as long as the candidate is correctly selected (04). However, access to surgical intervention for the treatment of epilepsy is highly variable between countries (64; 04; 67).

Availability of epilepsy surgery requires a specialized team consisting of an epileptologist, a neurosurgeon that specializes in epilepsy surgery, and technical services with, at minimum, video-EEG recording and an MRI (12; 04; 63). The success of epilepsy surgery depends on both the availability of the procedure and the accurate identification and selection of the surgical candidate. Even in industrialized countries, perhaps only 5% of potential surgical candidates are ever referred to an epilepsy surgery center. This is largely attributed to misinformation about the risks and benefits of surgery (12; 04; 62).

The use of more advanced and specific imaging techniques could be required in a significant number of surgical evaluations. These advanced techniques include positron emission tomography (PET), single photon emission computerized tomography (SPECT), and magnetoencephalography (MEG), which are rarely offered in low- and middle-income countries (08; 17).

Another pillar in the appropriate selection of a surgical candidate is neuropsychological testing. These services are available in only 37% of low-income countries and are available free of charge in about one third of these countries (64; 11).

In one study, epilepsy surgery was only offered in 22% of low- and middle-income countries, with the most common procedure being temporal lobectomy (67). Nevertheless, there appears to be an increasing trend of epilepsy surgery in Latin America and Asia. Epilepsy surgery programs are now widely found in Brazil, China, India, and Turkey and are being developed in many other countries with limited resources. Currently, surgical procedures in the appropriate candidate are considered to be a more cost-effective treatment than continued pharmacotherapy (12; 67).

Neurostimulation

Stimulation of diverse peripheral and central areas of the nervous system is one of the evolving approaches to the management of drug-resistant epilepsy (36). The techniques, which range in efficacy between 40% and 90% seizure reduction, include vagus nerve stimulation, deep brain stimulation, responsive neurostimulation, repetitive transcranial magnetic stimulation, and transcranial direct current stimulation (36; 33). The lack of trained physicians, limited understanding of the procedure, and the high costs of the devices and surgeries are some of the major obstacles for the accessibility and development of neurostimulation in low-income countries and low-income individuals in high-income countries (33; 73).

Ketogenic and other therapeutic dietetic options

An older, but successful, treatment for drug-resistant epilepsies is the use of diet therapies. The use of ketogenic diet has been studied since the 1920s and is now accompanied by investigations of the modified Atkins diet and low glycemic index diet (28; 54; 22). Most studies reported an average improvement of at least 50% in half of the patients treated with ketogenic diet (18; 22). Its application is associated with challenges, including accurate patient selection, close follow-up, and laboratory monitoring, as well as tolerance and poor compliance. It represents a lower cost and noninvasive management approach (45; 54). Other reported benefits of the diet include improvement in behavior, cognitive function, and mood (45; 22).

Conclusion

Throughout the years, the World Health Organization and other local and international agencies have made significant progress in defining the treatment gap in epilepsy and identifying its possible causes, and they have attempted to provide recommendations to reduce it. However, there is still much work to be done locally and internationally.

It is of utmost importance to identify the most prominent etiological factors in the population to treat, considering that causes of epilepsy in low- and middle-income countries could be preventable with appropriate public health measures, such as improvement of hygiene, vaccination, and early detection of infection in pregnancy (62).

The social stigma of seizures and epilepsy greatly contributes to non-acceptance of the diagnosis and its inadequate treatment. The use of creative strategies to educate the population, as well as to train healthcare providers, is warranted. The promotion of physical and digital publications written in simple language, as well as the use of technologic instruments and computer programs, are important. Among these, wearable devices and mobile applications could be paramount in the evaluation and treatment of epilepsy in the future. Of note, education regarding SUDEP syndrome could reduce early mortality, particularly in high-risk populations (35).

The substantial gap in epilepsy treatment could be addressed by effective public health policies directed towards the improvement of instruction and infrastructure, as well as universal access to specialized healthcare providers, diagnostic tools, and appropriate pharmacologic and surgical strategies (08). The use of technological resources to provide care, education, and treatment must be highlighted, and methods should be standardized.

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Contributors

All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.

Authors

Karla Mora Rodriguez

Dr. Rodriguez of the University of South Florida has no relevant financial relationships to disclose.
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Selim R Benbadis MD

Dr. Benbadis of the University of South Florida and Tampa General Hospital received honorariums from Catalyst, Jazz, LivaNova, Neurelis, SK Life Science, Stratus, and UCB as consultant, speaker, or advisory board member. He received grant support from Cerevel Therapeutics, Elsai, Jazz, LivaNova, Longboard, Marinus, Neuropace, SK Life Science, Takeda UCB, and Xenon Pharmaceuticals.
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Editor

John M Stern MD

Dr. Stern, Director of the Epilepsy Clinical Program at the University of California in Los Angeles, received honorariums from Ceribell, Jazz, LivaNova, Neurelis, SK Life Sciences, Sunovian, and UCB Pharma as advisor and/or lecturer.
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Former Authors

Manjari Tripathi MD
Michelle Braslavsky DO
Michael R Sperling MD

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Epilepsy: treatment in low and middle income countries

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Clinical Categories

Epilepsy & Seizures

Epilepsy: treatment in low and middle income countries …

Epilepsy: treatment in low and middle income countries

Introduction

Overview

Key points

A difficult dilemma

Magnitude of the burden

Etiological factors

Diagnostic aspects

Imaging

Electroencephalography (EEG)

New diagnostic technological aids

Therapeutics

Antiseizure medications

Epilepsy surgery

Neurostimulation

Ketogenic and other therapeutic dietetic options

Conclusion

References

Contributors

Authors

Editor

Former Authors

ICD & OMIM codes

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Also in This Category

Photosensitive occipital lobe epilepsy

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Epilepsy: treatment in low and middle income countries

Introduction

Overview

Key points

A difficult dilemma

Magnitude of the burden

Etiological factors

Diagnostic aspects

Imaging

Electroencephalography (EEG)

New diagnostic technological aids

Therapeutics

Antiseizure medications

Epilepsy surgery

Neurostimulation

Ketogenic and other therapeutic dietetic options

Conclusion

References

Contributors

Authors

Editor

Former Authors

ICD & OMIM codes

This is an article preview. Start a Free Account to access the full version.

Questions or Comment?

Also in This Category

Photosensitive occipital lobe epilepsy

Intermittent explosive disorder

Pyridoxine/P5P-dependent developmental epileptic encephalopathy

Reflex seizures

Anti-LGI1 encephalitis

Self-limited (familial) neonatal epilepsy

Epilepsy with auditory features

Alcohol withdrawal seizures

This is an article preview.
Start a Free Account
to access the full version.