The World Health Organization (WHO) reports estimate of about 50 million people worldwide have epilepsy – 80% of which reside in low- and middle-income countries (LMICs). There has been an increase in the burden of epilepsy worldwide over the past four decades with an increased prevalence of almost 11% from 1990-2021, with PWE in LMICs representing most of the epilepsy burden worldwide in terms of incidence, prevalence, fatality, and disability adjusted life years. It is estimated that seventy percent of people living with epilepsy (PWE) could live seizure free if accurately diagnosed and treated. There is a significant treatment gap – three-quarters of PWE living in low-income countries do not get the treatment they need. There is a need to provide better treatment and prevention, research on the risk factory of idiopathic epilepsy, long-term epilepsy surveillance, and exploration of effects on cultural differences and stigma surrounding epilepsy and epilepsy care (Tianqui 2025).

The economic strain on epilepsy in these LMICs includes direct costs to the healthcare system (e.g., ASMs), indirect costs to society (e.g., unemployment or disability) and intangibles (e.g., social stigma). There has been a direct correlation with increased costs associated with increased number of ASMs a patient is prescribed beyond the cost of the medication but also due to increased adverse events, treatment failures and lack of standardization and variability in practice (Yardi 2025). To manage refractory epilepsy in these settings, it is important to do more with less. Implementing strategies to mitigate gaps in training programs, development of standardized protocols, dietary therapies, cost-conscious presurgical evaluations as well as increasing appropriate access to medication through use of cost-effective ASMs and incorporating principles of rational polypharmacy. By addressing these gaps, LMICs can improve outcomes for individuals with medically refractory epilepsy and reduce the burden of untreated seizures on patients and healthcare systems worldwide (Yardi 2025).

While there is a growing number of international initiatives to mitigate these gaps including the Intersectoral Global Action Plan  (IGAP) on Epilepsy and Other Neurological Disorders –  with one of its  aims is to increase access to appropriate, affordable and safe ASMs for at least 80% of PWE worldwide by 2031. Strategies to utilize rationale polypharmacy in settings with limited resources include education of generalists and trainees, utilizing telemedicine consultations to bridge issues of access to specialized care, development of standardized protocols especially in conjunction with incorporation of principles of rationale polypharmacy considering local availability of therapies and technology, research and focus on improvement of clinical outcomes and quality of life (Yardi 2025). 

In addition to utilizing strategic combinations of medications through rationale polypharmacy – which is the use of two or more agents in combination to ideally achieve supra-additive efficacy, infra-additive toxicity and have compatible pharmacokinetic profile –  it is important to increase the range and affordability of medications through the use of generic medications as appropriate and prioritizing affordable (and sometimes even newer) first line agents based on seizure type. The cost of medication is not the only cost associated with the medication. Cost can also include adverse effects, toxicities, and laboratory monitoring–all of which sometimes when factored in lead to newer (and more expensive) ASMs being more cost-effective if available. Interestingly despite the increased use of generics in the past 20-30 years, the cost of ASMs has increased per person resulting in a generics paradox, even in the United States. Worldwide there are additional barriers to the use of generic medications and unfortunately the average retail price of ASMs is not significantly different across countries despite the difference in per capita income. While addressing these global barriers in the diagnosis and chronic management of epilepsy are important especially to prevent progression to hospitalizations and mortality, these barriers in LMICs are not unique to the chronic management of epilepsy. There is a similar burden of status epilepticus and barriers to medication access and specialized care in these resource limited settings.

Status epilepticus (SE) has a disproportionately high mortality risk in people with epilepsy (PWE) in low to middle income countries (LMICs) of about 2.6x (1.3- 7.2x) when compared to the general population. The reported annual incidence of SE is about 1.3 to 74 cases per 100,000 worldwide: an underestimation of the true burden due to SE due to the threshold of thirty minutes before classified as SE. In resource limited settings (RLS), the poor outcomes and inadequate treatment are due to lack of access, lack of education and lack of standardization.

A recent systematic review of the management of SE in adult patients residing in RLS was conducted including 23 studies in three continents with a total of 1526 patients, mostly in Asia with limited studies from Africa and Latin America. It was found that there is a highly variable, heterogenic diagnostic and management practices based on local availability of drugs and expertise as opposed to optimal guideline recommendations (Soni 2025).

Key results include that the most common etiologies were acute symptomatic and nonadherence to ASMs in more than half of patients. There was a lack of access to continuous EEG monitoring and mortality outcomes were 43% higher than in higher income countries (Soni 2025). While in most studies, benzodiazepines were given first line with or without another ASM, benzodiazepines used as first-line were variable in terms of agent and route and consistently were underdosed. Some studies included patients who received multiple benzodiazepines concurrently or in succession. Due to heterogeneity, no conclusion could be made regarding choice of benzodiazepine or ASMs and associated outcomes.

The use of older second-line ASMs were widely utilized, with the most common being valproic acid, phenytoin, and phenobarbital. The use of levetiracetam was also common especially after the update of the World Health Organization's Essential Medication List in 2023 where levetiracetam was added as an essential antiseizure medication. Other ASMs on this list include lamotrigine, carbamazepine, phenobarbital, phenytoin and valproic acid. The use of oral ASMs for SE was common. One study investigated the costs associated with SE and found that when comparing costs of oral vs intravenous levetiracetam and valproic acid, the intravenous solution cost is more than 300 times the oral medication, leading to a much larger cumulative cost. This is especially detrimental to these patients as these medication costs are borne primarily by the patients and their families. To optimize the emergency management of status epilepticus in resource limited settings, it is important to increase access to (1) specialized training through telemedicine consultations, education, and training, (2) essential and cost-effective ASMs (3) standardization of best practices.

Education and Training

“Education is the most powerful weapon which you can use to change the world,” Nelson Mandela words are especially true in healthcare. To bridge the gaps in these disparities worldwide, the first step is awareness. Patients, their families, the public, government agencies, and healthcare workers alike should all be educated on epilepsy and status epilepticus. Generalists and trainees should be educated to develop a system of paying it forward. It is important to not underestimate the power of the fundamentals which are building blocks of innovation.

A solid understanding of the pathophysiology of epilepsy and neuropharmacology allows for clinical deductive reasoning, which is often required in emergency management in limited resource settings. Timely administration of appropriately dosed, prehospital benzodiazepines should unequivocally be the standard. Healthcare providers and government agencies should be made aware of the latest evidence and best practices to implement at their local institutions and expand access to the essential medications and technology in their respective regions and countries. Ignorance is no longer a justification but rather a choice in the world we live in.

Standardization & Best Practices

The lack of protocols that are adapted to local contexts to guide effective and timely interventions is often cited as a major contributor to poor outcomes in conditions such as status epilepticus in resource limited settings. Development of standardized protocols to aid generalists for best practices is necessary. The collaboration between local clinicians and consulting specialists is vital to the development beyond internationally published guidelines. Telemedicine can be utilized for expert consultations in areas with limited access to bridge these issues of access to specialized care. The development of such institutional standardized protocols and operationalization of best practices such as prehospital emergency services or accurate diagnostic criteria of SE vs prolonged nonepileptic seizures is paramount to the clinical outcomes of these patients. In addition to optimizing clinical outcomes, it is important to remember patients are humans. Improving outcomes such as quality of life are just as equally important if not more so, than focusing solely on improving objectively clinically significant outcomes such as seizure control.

Expanded Access

Initiatives focusing on education and standardizations of best practices can improve care in resource limited settings in a timely manner. However, more importantly, it will provide the foundational awareness for necessary changes in international health policy to ensure the provision of essential resources – such as safe, high-quality, and cost-effective ASMs – for the diagnostic and treatment of patients worldwide. As members of a society dedicated to the service to patients within the field of neurocritical care, it is our responsibility to do our part – as individuals, as a profession and as a society.

CALL to Collabor-ACTION

While these overarching strategies seem simple, they require intensive effort, resource, and commitment. Over the past few years, it has been my mission to do my part as an individual by spreading awareness, increasing the dissemination of my scarce and unique expertise in pediatric neuropharmacology and neurocritical care pharmacotherapy through education and increasing access to specialized care by providing telemedicine consultations worldwide. However, there is strength in numbers. My call to action is seeking collaboration. If this is an initiative that tugs at your heart strings or stirs your passion to act , please support my mission – no child, or rather no human should receive anything less than the best clinical care – especially not  because of who they are or where they live.