For eight years, Scott Badzik of Loveland, OH, flew 767s for Delta Airlines. Then, in 2005, he took a long run on a hot day, came home, took a shower, and was walking down the stairs when he suddenly started to feel odd. He noticed his vision changing; it seemed like he was looking through a prism. He suddenly collapsed. He was unconscious and had violent muscle contractions: a seizure. His wife immediately called 911. He had another seizure just after the paramedics arrived.

After having an MRI, CT, and PET scan, Badzik underwent a brain biopsy and was found to have encephalitis, or inflammation in the brain. At that point, Badzik was referred to a neurologist. "It was at my initial appointment with my neurologist that I first heard the word 'epilepsy,'" he recalls. Later, an electroencephalogram (EEG), which measures electrical activity in the brain, confirmed that his seizures were originating from the area of his brain where the inflammation occurred.

Epilepsy 101

Badzik is one of at least 3 million adults and nearly 500,000 children in the United States with some type of epilepsy, in which seizures are caused by abnormal electrical discharges in the brain, according to the US Centers for Disease Control and Prevention. The condition has various causes, including infection, traumatic brain injury, abnormal brain development, an imbalance of neurotransmitters (nerve-signaling chemicals), dysfunctional brain wiring or abnormalities in brain cells, genetic abnormalities, stroke, or a combination of these and other factors. For more than half of those with epilepsy, the cause is unknown, according to the Epilepsy Foundation.

Among children, those with developmental and neurologic disorders, such as cerebral palsy, autism spectrum disorder, Down syndrome, and tuberous sclerosis complex (TSC), a genetic condition that causes benign tumors to develop in the brain and other areas, are most likely to have seizures.

Seizure Types

Seizures are loosely divided into two types: focal onset and generalized onset, says David Spencer, MD, FAAN, professor of neurology and director of the Comprehensive Epilepsy Center at Oregon Health & Science University in Portland. He is also the author of Navigating Life with Epilepsy (Oxford University Press, 2016), part of the American Academy of Neurology's Neurology Now™ Books series. 

Focal onset means the seizures start in a network of cells on one side of the brain, while generalized onset means they involve networks on both sides of the brain. These seizures are categorized further to describe the patient's level of awareness (impaired or not) and accompanying motor symptoms (jerking, stiffness, or loss of muscle tone) and/or non-motor symptoms such as a blank stare, problems talking or understanding others, and changes in heart rate, breathing, and complexion.

In Badzik's case, he had a generalized tonic-clonic seizure, which means he lost consciousness and exhibited muscle stiffness (referred to as "tonic") and muscle jerking (known as "clonic"). These types of seizures can begin in one half of the brain and spread to both halves, as in Badzik's case. Or they can begin suddenly and simultaneously in both halves of the brain, says Dr. Spencer.

Treatment Options

Once a person has been diagnosed with epilepsy—which typically involves blood tests, an EEG, and brain scans such as an MRI or CT—the first line of treatment is an antiepileptic drug (AED), says Dr. Spencer. The neurologist first identifies the type of seizure, then chooses the group of medications that best match that seizure type. From there, the neurologist can customize the treatment regimen even more, says Dr. Spencer. The goal is to pick the most effective drug with the fewest side effects. "You have to have a plan B and C, in case the first drug isn't effective enough or causes problems."

That has been Badzik's experience. He was initially prescribed the anticonvulsant lamotrigine (Lamictal). Since then, he and his neurologist have experimented with different drugs, doses, and devices to find the right balance between control of his seizures and side effects. He currently uses a vagus nerve stimulator, a device that sends regular pulses of electrical energy to the brain via the vagus nerve, in addition to medication. He no longer has generalized tonic-clonic seizures, but he continues to have focal-onset impaired awareness seizures, which are often preceded by a warning, or aura—changes in vision or a sense of deja vu—and during which he may have impaired consciousness for one to two minutes.

Badzik, who no longer drives or flies planes, has also found exercise to be helpful in reducing the frequency of his seizures. At first his neurologist was wary, mainly because there isn't enough literature on the benefits of exercise for epilepsy. He was also concerned about Badzik's safety, but after he and Badzik established certain precautions—for example, using smartphone and GPS technology that can alert others if Badzik has a sustained seizure during a run—Badzik has resumed long-distance running, cycling, and regular visits to the gym. 

More Medication Options

Several medications have been approved for teens and adults with epilepsy, including brivaracetam (Briviact), perampanel (Fycompa), and lacosamide (Vimpat). "We still don't have a medication that will stop seizures in 50 percent of people who have failed to respond to the first medication they have tried, but every new medication seems to benefit some people, and some offer fewer side effects," says Michael D. Privitera, MD, professor of neurology and director of the Epilepsy Center at the University of Cincinnati.

Researchers also continue to evaluate the potential effectiveness of cannabidiol, a non-psychoactive form of cannabis, which appears to have anticonvulsant properties. In one trial of patients with a severe form of epilepsy who had experienced at least two atonic seizures—also known as drop seizures, in which patients lose muscle tone and go limp for 15 seconds—per week and had failed to improve on at least one AED, cannabidiol was shown to reduce monthly atonic seizures by 44 percent. All patients continued to take their regular medication during the trial. The results were presented at the 2017 Annual Meeting of the American Academy of Neurology (AAN) by Jacqueline French, MD, FAAN, professor of neurology at the New York University Comprehensive Epilepsy Center and chief scientific officer for the Epilepsy Foundation. Dr. French receives personal compensation from GW Pharmaceuticals, which supported the study.

Short-Circuiting Seizures

Researchers are now focusing on how epilepsy develops, with the goal of identifying treatments that will specifically stop or reduce seizures, says Vicky Holets-Whittemore, PhD, program director in the Channels, Synapses, and Circuits Cluster at the National Institute of Neurological Diseases and Stroke (NINDS) in Bethesda, MD. "We are moving toward precision medicine, where we have a targeted treatment for a targeted cause."

Some of the best clues are coming from research on tuberous sclerosis complex (TSC), she says. "There are early predictors of who will and won't have seizures." Researchers are currently trying to determine how to inhibit the mTOR pathway, a "master regulator" of cell growth and metabolism in the nervous system in some acquired and genetic forms of epilepsy, in order to prevent seizures related to TSC, she says.

In another presentation at the 2017 AAN Annual Meeting, David N. Franz, MD, founding director of the Tuberous Sclerosis Clinic at Cincinnati Children's Hospital, reported on the effectiveness of everolimus (Afinitor), an oral drug developed to treat cancer and an mTOR pathway inhibitor, in treating patients with medication-resistant TSC. Those who took the highest dose of the drug saw a reduction in seizure frequency by 40 percent. In fact, Dr. Franz noted, the longer patients were on the drug, regardless of dose, the better the response.

The study showed for the first time that a medication could change the mechanism behind the seizure, in this case by reducing the overactivity of the mTOR pathway, says Dr. Franz, who accepts payment for consulting work, research grants, speaking engagements, and travel from Novartis, who sponsored the study. Everolimus appears to desensitize the cells in that area, making them less likely to trigger a seizure, he says.

Researchers are also studying how disruptions in cell membranes let molecules such as sodium, calcium, and potassium enter the cells, generating electrical impulses associated with epilepsy. And they're looking at whether inflammation and the body's immune system impair brain receptor function, which may cause abnormal nerve cell activity. Other studies are examining how problems associated with the blood-brain barrier may allow certain proteins to migrate into the brain, causing neurons to become hypersensitive and trigger seizures.

More Precise Medicine

In 2007, the NINDS established the Epilepsy Phenome/Genome Project (EPGP), a consortium of 27 epilepsy centers in the United States, Canada, Argentina, and Australia. Since then, the project has enrolled more than 4,000 people with epilepsy, along with healthy controls, in order to pinpoint genetic factors associated with various forms of epilepsy. Participants provide blood samples and information about their seizures and treatment; they also undergo an EEG and neuroimaging tests. The EPGP is now part of the "Epilepsy Center Without Walls," also funded by the NINDS, which aims to modify the course of the disease and prevent its development in people at risk.

The EPGP has found many more genetic mutations associated with epilepsy than expected, says Dr. French. It also has revealed that people can have a spontaneous novel or de novo mutation—and thus have a genetic link to epilepsy—without having a mother or father with the disease. That is, genetic does not always mean inherited.

The rapidly expanding genetic knowledge base helps support the development of targeted and potentially precision-based therapies, Dr. French says.

To that end, researchers are subdividing seizures into smaller subsets that may have common causes, says James W. Wheless, MD, FAAN, professor and chief of pediatric neurology at the University of Tennessee Health Science Center in Memphis. This progress is being accelerated through collaboration between research centers and through faster, less expensive genetic screening techniques. Precision medicine uses information about an individual's genetic predisposition to epilepsy and how he or she metabolizes and responds to medication to fine-tune their treatment, Dr. Wheless explains.

A Supportive Network

For Badzik, the former airline pilot, the biggest lesson he's learned from his diagnosis is that he can lean on others for help. "At first I tried to white-knuckle it, to manage epilepsy on my own," he says. "But when one person is diagnosed with epilepsy, the whole family has epilepsy." Participating in an adult support group, volunteering at an epilepsy camp, collaborating with his physicians, and opening up to his wife, family, friends, and even strangers, has helped him adapt.

"The Sherpas do all the work for people climbing Mount Everest," says Badzik. "I'm so grateful for all the Sherpas in my life—the people looking out for me every time I run or bike or go to the gym."

Resources

• American Epilepsy Society: 312-883-3800
• Citizens United for Research in Epilepsy: 312-255-1801
• Epilepsy Foundation: 800-332-1000
• International League against Epilepsy: 860-586-7547
• National Institute of Neurological Disorders and Stroke: 800-352-9424