Epilepsy has been tied to evil spirits and mystery as far back as the days of Mesopotamia. That cradle of civilization knew nothing about neurons, synapses, and electrical pulses.
Later, Hippocrates of ancient Greece attributed the illness to the brain, though his ideas would not gain general acceptance for many centuries. In addition to being associated with witchcraft, some people believed epilepsy was contagious and could be transmitted through saliva — which it is not.
Even Ohio has its place in the long history of epilepsy. In 1893, Gov. William McKinley, whose wife suffered from epilepsy, declared the opening of a hospital offering living arrangements and the most-up-to-date care. Located in Gallipolis in extreme southeastern Ohio, it was the first specialized epilepsy colony in the United States and the first publicly-funded facility in the world.
The long-recognized malady is a worldwide phenomenon that inflicts its victims with seizures that can last a few seconds to a few minutes. There may be a nearly undetectable staring off into the distance, or a jerking of the arm, or uncontrolled shaking of the entire body, according to Crystal Hall, a regional director of the Epilepsy Foundation in Ohio.
Ms. Hall describes epilepsy as a malady like diabetes, which has subsets and different types. There can be genetic predispositions, head trauma, and associations with stroke in older people, and autism in younger folks. There may not be a known cause.
“That is the $1 million question,” said Dr. Imad Najm, director of Cleveland Clinic Epilepsy Center. “The answer is there are many causes that we know, and there are many causes that we do not know.”
While evil spirits have been discounted, some mysteries still remain.
Epileptic seizures can result in damage to the brain, which is why it is best for the 3.4 million people in the United States with some form of epilepsy to get a handle on the malady as soon as possible.
“Every time there is a seizure, there is small damage to the brain,” Dr. Najm said.
The seizure loop
Only a very small percentage of neurons show changes after an epileptic seizure in mice, but these alterations can be permanent and trigger future seizures that can affect the whole brain and lead to impaired cognition, including memory and learning, according to new research from the Perelman School of Medicine at the University of Pennsylvania.
“It is clear there is some connection between an epileptic brain, impaired memory, and trouble controlling emotions and how we act on those feelings, but we don't understand the underlying mechanisms,” said Dr. Frances E. Jensen, chair of the Department of Neurology and senior author of the study, which was published in March.
Epilepsy is characterized by excessive activity of brain cells — neurons — which generate seizures. Research is increasingly showing that the development of epilepsy involves changes in the synapses, which are structures that connect one neuron to another.
“The overactive neurons lose their ability to build the strong synapses necessary for learning, which may explain why some people with epilepsy have trouble with learning and with memory,” Dr. Jensen said. “If we can stop these neurons from undergoing changes after being activated by seizures, our hope is that we can also prevent not only the progression of epilepsy, but also avoid these cognitive deficits individuals experience long-term.”
The World Health Organization estimates that 50 million people worldwide live with epilepsy, but cautions that a single seizure does not indicate one has the disorder. It further estimates that up to 70 percent of people living with epilepsy could become seizure free with appropriate use of antiseizure medicines. “Discontinuing antiseizure medicine can be considered after 2 years without seizures and should take into account relevant clinical, social and personal factors,” the WHO notes on its website.
Know the triggers
Diagnostic evaluations include genetic testing, and more sophisticated brain imaging, according to Dr. Imran Ali, professor of neurology and interim dean at the University of Toledo’s College of Medicine and Life Sciences.
“Treatments are being developed for specific types of epilepsies, and medications are safer and less likely to cause side effects as in the past,” he said. “Surgical treatments are more focused and associated with excellent outcomes even in very refractory cases.”
Missing a dosage of medication is one of the biggest triggers for a seizure, according to Ms. Hall. But there are lesser, often genetically linked triggers, including flashing lights and some sounds. One trigger has come to the forefront in a recent study that identifies unusually hot days as a growing concern in light of climate change.
“Some of our patients tell us they will have more seizures if the weather is too hot or they have been outside all day long,” Dr. Najm said. “It is very important to know these triggers.”
Other triggers can include flashing lights, particular sounds, or lack of sleep. Extremes in blood sugar, a fever, dehydration, and hormonal changes, such as during menstruation, also can be triggers.
“Anything that creates an irritation will make these neurons itchy and may create a seizure,” said Dr. Najm, adding that there are hundreds of different causes, including inflammation or changing potassium levels.
Treatment options
“Epilepsy is a treatable condition; more than 20 medications have been approved for treatment of epilepsy, and approximately two-thirds can be controlled with either a single medication or a combination,” Dr. Ali said.
Phenobarbital is one of the oldest medications to be used and is still administered today, according to Dr. Najm.
For the third of patients in which medications do not fully control seizures, the next step is to try the various kinds of implants to direct small electrical charges to the brain that dilute or completely end seizures.
For the small percentage of patients who still suffer from uncontrolled seizures, surgery to remove the small portion of the brain, if it can be located, has seen successful. Also, laser treatments are being used to burn out those pinpointed portions.
Dr. Najm has been involved in research that uses gene therapy, which has not yet been approved by the FDA, for these toughest cases.
“It is going to be much more used in the future,” he predicted.
This method involves using an inactive virus to deliver a modification that will shut down the misbehaving neurons responsible for seizures. In this manner, no brain function will be lost.
“One seizure is one too many,” Dr. Najm said. “The goal is to completely shut down the seizures.”
First Published January 19, 2025, 5:00 a.m.
