Understanding Post-traumatic Epilepsy

It is my great pleasure to be with all of you today talking about post-traumatic epilepsy. I will try to be as simple as possible, but not simplistic.

First of all, what is a seizure, what happens in the brain of someone who has a seizure, and what is the difference between having a seizure and having epilepsy? Many of you may have an idea what a seizure is because they know someone who has epilepsy or they may have seen it. The brain is like the computer of the body, the electric system of the body. Everything runs through electrical signals, and an epileptic seizure is simply an electrical shortcut happening in the brain, in one area of the brain, or involving the whole brain. Having an isolated seizure is not that uncommon. It is estimated that up to 5% of the population can have a seizure during their life.

Epilepsy is different. The International League Against Epilepsy published a practical definition in 2014. Epilepsy is the enduring predisposition of the brain to having repeated seizures. This predisposition has been quantified as a risk higher than 60% of having a second seizure after the first one in the subsequent two years. This 60% is on a balance high enough to recommend taking anti-seizure medications. Based on this, one in 26 people in the world have epilepsy; that is 50 million people worldwide.

In traumatic brain injury, the situation is more complex because seizures may represent the symptom of the underlying brain insult. Shortly after a head injury, people may have a seizure; these are called early seizures, or acute symptomatic seizures. They are a symptom of the brain insult and they do not represent the onset of epilepsy. There are then other seizures happening later on called late seizures, and they are the consequence of a number of chemical and structural changes in the brain that lead to this enduring predisposition. Scarring in the brain or other reorganization of networks accounts for this, and this is post-traumatic epilepsy.

At the moment, everyone identifies seven days as the cutoff to distinguish between early and late seizures. Early seizures are not associated with an increased risk of having subsequent seizures, so they do not represent post-traumatic epilepsy. But when they happen, it means that the head injury is serious. Having an early seizure is associated with an increased risk of dying because of the severity of the head injury in the subsequent 30 days. This is why doctors sometimes decide to start the patient on anti-seizure medications early to minimize risk. These medications should be gradually stopped when the patient is more stable.

The problem of post-traumatic epilepsy is that, unfortunately, seizures can start at any time. There are observations of patients that have developed them after a decade or two, possibly because the brain's rewiring may be less efficient as we age. Post-traumatic epilepsy is a symptom of the severity of the head injury; it happens rarely in a mild head injury and more frequently in someone who had a very severe injury with a skull fracture or a lesion.

Is it possible to prevent the development of post-traumatic epilepsy by giving medications immediately? At the moment, no. In the last 35 years, researchers have tried many compounds, but none have managed to stop the changes that lead to post-traumatic epilepsy. Anti-seizure medications do not prevent it because they simply help electricity run smoothly; they are not neuroprotective agents.

Having a head injury means a lot in terms of brain performance. The development of post-traumatic epilepsy represents a second hit, as the brain has to find a new baseline to function. Controlling seizures completely is the best way to help the brain find a new balance.

Why do we treat epilepsy? The main reason is SUDEP, or Sudden Unexpected Death in Epilepsy. This is a category of uncommon sudden death where a person otherwise healthy dies unexpectedly. It is not frequent—one out of 1,000 people with epilepsy dies of SUDEP each year—but it is very relevant. We know from research that the electrical disruption involves key areas responsible for breathing control that can happen during or shortly after a seizure.

The most relevant risk factors are having grand mal seizures, especially during sleep. Being a young man with early-onset epilepsy, not taking medications, and using alcohol or recreational drugs are also relevant risk factors. Everyone can lower the risk by taking medications regularly, getting enough sleep, avoiding substances, and working with a doctor to achieve better seizure control. Room sharing is also a significant prevention factor for SUDEP.

How do we treat post-traumatic epilepsy? We have anti-seizure medications as the first-line treatment. Epilepsy surgery is a valuable option, as is neurostimulation, specifically vagus nerve stimulation. Ketogenic diet is another option, though less used in adults. There are also new compounds under investigation, including stem cell transplants. Unfortunately, it is not possible to predict which drug is best for an individual. Around 30% of patients become seizure-free on the first drug; another 30% become free on a second option or combination; and 40% have drug-resistant epilepsy. The approach is through trial and error.

For those who are drug-resistant, epilepsy surgery involves removing the area of the brain responsible for the electrical shortcut. While head injury patients are not always considered immediately due to potential complexity, it is always worth discussing with your doctor. Neuromodulation, like vagus nerve stimulation, is also a valid option that resettles the electrical activity of the brain.

50% of adults with epilepsy have at least another medical condition, or comorbidity. People with post-traumatic epilepsy have to face a variety of problems at the same time: psychological consequences like anxiety, depression, post-traumatic stress disorder, cognitive problems, and sleep issues. This is why a multidisciplinary approach is important. There is a lot that patient associations can do, primarily through education and advocacy.

To conclude, post-traumatic epilepsy represents one in five of all symptomatic epilepsies and one in 20 of all epilepsies. The good news is that more than half of patients can be completely seizure-free on medications. For those that don't respond, there are alternative options.

(Introduction to the Epilepsy Research Institute)

My name is Laura Price, and I am the research program manager at the Epilepsy Research Institute. We were originally Epilepsy Research UK, and in 2023 we were granted institute status to drive research in the UK. Epilepsy is a hugely complex area, and there are many conditions that can give rise to it, including structural, metabolic, infectious, immune, and genetic causes.

We conducted a priority-setting partnership with the James Lind Alliance, asking people who live with epilepsy, health professionals, and researchers to identify the most important unanswered questions. We refined these into a top 10 list of priorities, which has shaped our research program into four main areas: neurodevelopment; advanced therapeutics and disease modification; mortality, morbidity, and risk; and reproduction and hormones. We also have two cross-cutting themes: enabling technologies and capacity building.

For each theme, we have theme leads supported by a task force of experts, including people with lived experience through our Shape network. We currently have 716 people signed up to our Shape network who become involved directly in research. We share opportunities with them to comment on studies and help scientists shape their research. Finally, I want to draw your attention to a wonderful short film made by a young man with epilepsy in 2018 called 'Under the Lights,' which provides an insight into the impact of seizures on a young person's life.