APPROXIMATELY 30 TO 40 PERCENT OF EPILEPSY PATIENTS ARE TREATMENT RESISTANT and live with uncontrollable seizuresAccording to an Institute of Medicine report, this group is also at a higher risk of mortality, having a 20 times higher rate of sudden unexpected death compared to the general population. The most catastrophic forms of epilepsy occur in very young children and have a lifelong negative impact on patients, families, and communities.

We have developed this Epilepsy Giving Smarter Guide with the express purpose of empowering patients, supporters, and stakeholders to make informed, strategic decisions when directing their philanthropic investments and energy into research and development efforts.

 

 

 

 

 

 

EXECUTIVE SUMMARY

One in twenty-six Americans has epilepsy, a condition characterized by unprovoked and recurrent seizures. At least 50 million people live with this disorder worldwide according to the World Health Organization. The manifestation of epilepsy, in terms of seizure type, severity, and age of onset, varies widely among patients. Just like there are many different cancer subtypes and severities that require tailored individualized treatment, epilepsy is beginning to be viewed as having many subtypes. Unfortunately, the biological and clinical profiles of all epilepsy subtypes are not well known. Although these profiles are difficult to elucidate, a focused effort to comprehensively identify and characterize epilepsy subtypes using precision medicine would greatly improve clinicians’ ability to diagnose and treat patients based on their epilepsy type.

Thirty to forty percent of epilepsy patients do not achieve effective seizure control with currently available therapies. Those who do achieve seizure control are often left to contend with severe adverse side effects from epilepsy therapies, comorbid conditions such as depression and anxiety, sleep disorders, learning and memory problems, increased suicide risk, and public misunderstanding and discrimination. If seizures remain uncontrolled, patients often experience lifelong disability. Supporting the expansion or development of accredited epilepsy centers with coordinated medical care teams would substantially improve comprehensive holistic care.

There are no disease-modifying therapies for epilepsy. Current epilepsy medications do not treat the underlying cause of epilepsy, but instead treat seizure, which is a symptom of epilepsy. Knowledge gaps in understanding of the biological underpinnings of epilepsy are currently precluding the field from developing treatments that can correct the abnormal biology that drives the disease. These fundamental knowledge gaps, along with the high cost of clinical trials and competing priorities, have weakened the value proposition for the pharmaceutical industry to invest in the development of new epilepsy therapies that can treat the disease and not only the symptoms. Strategic philanthropic support for basic and translational research to close the aforementioned knowledge gaps could incentivize the industry to pursue novel therapeutic targets.

Epilepsy is underfunded. Compared to other neurological diseases, government funding and nonprofit support has lagged behind. For example, epilepsy is six times more prevalent than Parkinson’s disease, but receives 10 times less funding from nonprofit and government funding sources combined. Additional funding and opportunities to attract young investigators and to encourage collaboration among the different research communities would ensure a sustainable and thriving workforce. The Milken Institute Center for Strategic Philanthropy has developed this Epilepsy Giving Smarter Guide with the express purpose of empowering patients, supporters, and stakeholders to make informed, strategic decisions when directing their philanthropic investments and energy into research and development efforts.

OVERVIEW

Epilepsy is a neurological condition characterized by seizures. Due to the range of differing seizure types and numerous causes, epilepsy comprises a spectrum of syndromes (referred to as the epilepsies) that affect patients and their families to varying degrees.

According to the Centers for Disease Control and Prevention, about 5.1 million people have received a diagnosis of epilepsy or a seizure disorder, making it one of the most common neurological disorders in the United States. The World Health Organization estimates that about 50 million individuals worldwide are diagnosed with epilepsy and that those at the lowest income levels bear a disproportionate burden of this disorder.

It is estimated that 60 to 70 percent of people with epilepsy can control seizures with existing treatments. However, for many of these patients, epilepsy remains a lifelong condition that requires combinations of up to six medications at a time. Moreover, the medications can have potential life-altering side effects ranging from dizziness, nausea, and fatigue to memory loss, liver toxicity, kidney dysfunction, bone loss, and brain atrophy. For pregnant woman, some medications can cause life-threatening birth defects in their unborn children. Furthermore, even though their seizures may be under control, patients often struggle with comorbid conditions such as depression and anxiety, sleep disorders, and learning and memory challenges. They are at risk of early mortality, especially from suicide, struggle for access to high-quality healthcare in neurology and other specialties, and are the victims of public misunderstanding and discrimination.

Approximately 30 to 40 percent of epilepsy patients are treatment resistant and live with uncontrollable seizures. According to an Institute of Medicine report, this group is also at a higher risk of mortality, having a 20 times higher rate of sudden unexpected death compared to the general population. The most catastrophic forms of epilepsy occur in very young children and have a lifelong negative impact on patients, families, and communities.

The ultimate goal is to develop better therapeutics that eliminate seizures and side effects for all people living with epilepsy.

SOCIETAL IMPACT OF EPILEPSY

Although epilepsy is a physical disorder of brain function, it often carries with it a substantial social burden that includes unemployment and uncertainties about future employment, low income and social isolation. Moreover, there can be questions about independent living, driving limitations, and stigma for those whose seizures can be managed, and debilitating, lifelong disability for those whose seizures cannot be controlled. One-third to one-quarter of children diagnosed with epilepsy will have an associated intellectual disability or learning disorders. Furthermore, people with epilepsy are three times more likely to commit suicide compared to the general population. The risk for suicide increases to fivefold among newly diagnosed patients.

The total direct and indirect costs of epilepsy in the United States is about $19.7 billion per year. This estimate is based on a total cost of $12.5 billion calculated in 1995 and converted to 2016 dollars using Bureau of Labor Statistics data.

Figure 1. Government funding for epilepsy compared to other common neurological disorders (figure reprinted with permission from Macmillan Publishers Ltd: Nature, 2014). Source

Figure 1. Government funding for epilepsy compared to other common neurological disorders (figure reprinted with permission from Macmillan Publishers Ltd: Nature, 2014). Source

Although epilepsy is among the most common neurological disorders and its associated economic costs are high, United States government investment in epilepsy research is modest. Funding for epilepsy has lagged behind that for other common neurological conditions. For example, epilepsy is six times more prevalent than Parkinson’s disease and multiple sclerosis, but the three diseases receive similar amounts of funding (see Figure 1). 

 

 

CHARACTERISTICS OF EPILEPSY

The nerve cells in our brain communicate through electrochemical inputs. When this communication is disrupted by sudden intense bursts of electrical energy, a person experiences a seizure. Depending on where the disruption in communication occurs, the seizure manifests itself through a range of sensations, behaviors, movements, and/or loss of consciousness that differ in severity and frequency. Seizures can be non-convulsive and convulsive. Typically, a seizure will last from a few seconds to a few minutes. Prolonged seizures or clusters of seizures increase the risk of permanent brain damage. Therefore, a convulsive seizure that lasts longer than 5 minutes is deemed to be a serious medical emergency and is termed Status Epilepticus.

One out of 10 individuals will experience at least one seizure in their lifetime. A seizure is an event, while epilepsy is a disease that involves recurrent unprovoked seizures. One in 26 Americans has or will develop epilepsy. 

Figure 2. Side view of brain with the red bull’s eye indicating the source of seizure. A focal (partial) seizure can be pinpointed to one location vs. a generalized seizure, which cannot be localized to one specific location. (Adapted from © Alila07 | Dreamstime.com. Partial and Generalized Epilepsy Photo). Source.

Figure 2. Side view of brain with the red bull’s eye indicating the source of seizure. A focal (partial) seizure can be pinpointed to one location vs. a generalized seizure, which cannot be localized to one specific location. (Adapted from © Alila07 | Dreamstime.com. Partial and Generalized Epilepsy Photo). Source.

 

TYPES OF SEIZURES— FOCAL VS. GENERALIZED

There are many different types of seizures, but they can be grouped into two broad categories: focal versus generalized. Generalized seizures result from abnormal seizure activity occurring on both sides of the brain over large areas, while focal seizures (previously called partial seizures) result from abnormal activity in just one area of the brain (see Figure 2).

Generalized Seizures

Generalized seizures are disruptions in the brain network that involve both sides of the brain and can result in loss of consciousness, falls, or massive muscle contractions. These types of seizures are further classified into six categories:

  • Absence: In an absence seizure, the person “spaces out” for a short period of time. Unlike daydreaming, these seizures can occur during physical activity and cannot be interrupted. These seizures are most commonly seen in children ages 4-14 years.
  • Atonic: In an atonic seizure, a muscle (or muscles) suddenly loses strength. These seizures are sometimes called drop attacks because the person seizing may suddenly drop something or fall to the ground. These seizures are often brief, but, depending on where and how the person falls, serious injury can occur. This seizure is most often seen in childhood-onset epilepsies. 
  • Tonic: In contrast to an atonic seizure, in a tonic seizure, the muscle increases in tone and the body or limbs make sudden stiffening gestures. These seizures are commonly observed during sleep and usually last fewer than 20 seconds. 
  • Clonic: Clonic seizures are repeated rhythmic jerking movements of the arms and legs, sometimes on both sides of the body, which cannot be stopped by restraint. Pure clonic seizures are rare to observe, and often are seen with other seizure types. 
  • Myoclonic: Myoclonic movements are brief, shock-like jerks of a muscle or group of muscles that usually last 1-2 seconds. Many individuals have experienced a myoclonic movement or jerk when hiccupping or falling asleep. In epilepsy, myoclonic seizures usually cause abnormal movements on both sides of the body at the same time. 
  • Tonic-Clonic: This is the seizure type most often portrayed in media and was previously called a grand-mal seizure. The person seizing will lose consciousness and fall. The muscles stiffen (tonic aspect) and then jerk (clonic aspect). The seizure is also associated with a “cry” as the diaphragm muscles contract and the air in the lungs is exhaled. These seizures usually last 1-3 minutes and require a longer recover period.

Focal Seizures

Around 60 percent of people living with epilepsy will have focal seizures, which are localized to a specific focal area on one side of the brain. The type of focal seizure is often described by the area in which it originates. Depending on where the seizure is localized, it can manifest in different ways, ranging from motor, sensory, autonomic, or psychic symptoms. If areas involved in alertness and awareness are impacted, then loss of consciousness may occur.

The types of seizure symptoms are as follows:

  • Motor Focal Seizures: These seizures impact muscle activity on one side of the body, resulting in abnormal stiffening or jerking movements of a limb.
  • Sensory Focal Seizures: These seizures impact the senses. People may smell or taste things that are not there, hear ringing, see a spot of light, or feel a numb sensation.
  • Autonomic Focal Seizures: These seizures impact the parts of the nervous system that automatically control body functions, resulting in strange stomach sensations, changes in heart rate/breathing, goose bumps, and sweating. 
  • Psychological Focal Seizures: These seizures impact how people think or experience events, resulting in suddenly feeling a range of emotions such as fear or happiness without reason or experiencing difficulties with memory or understanding of language. Some psychic seizures result in the feelings of deja-vu (i.e., “I have experienced this before”) or jamais vu (i.e., “I have never been here even though the setting is actually familiar”).

A focal seizure may spread to the other side of the brain to become a generalized seizure. These events are termed as secondarily generalized seizures.