Wildfire in the brain: What has neuroscience learned from studying epilepsy?

October 22nd, 2024

Written by: Barnes Jannuzi

In your head right now, billions of electrical and chemical pulses are exploding every second. While the scale of this activity may seem chaotic and random, it is anything but… usually. There are numerous checks and balances in the brain that make sure it remains in a controlled state. If this balance fails and there is too much uncontrolled activity in brain cells, it can lead to a chain reaction where those overactive cells cause other cells to become overactive. This can quickly spread like wildfire in the brain, halting normal brain activity. This is known as a seizure, and repeated seizures are the hallmark of a disorder called epilepsy.

 Epilepsy affects more than 50 million people¹ worldwide and often has profound and debilitating effects on the safety and quality of life of patients. Because epilepsy is so common, impactful, and has a clear link from brain dysfunction (a seizure) to clearly definable symptoms, the study of this disorder has been a cornerstone of neuroscience. This article will explore 1) what we have learned about epilepsy, 2) treatment options available to individuals with epilepsy, and 3) important insights into how brains work that were only made thanks to the participation of individuals with epilepsy.

What is Epilepsy?

Epilepsy is, unfortunately, not just one thing. It is an umbrella diagnosis given to anyone who suffers from multiple seizures. Some of the more common causes of epilepsy are from brain damage (e.g. a complication during birth, a tumor, head injury, or infection) or a genetic condition (e.g. mutations in the genetic code of an individual which affect the activity of the brain cells)². 

Additionally, two people with epilepsy will not necessarily have the same kinds of seizures. One of the most common seizure types depicted in media is a tonic-clonic seizure where the individual’s muscles stiffen and jerk violently as they lose consciousness. But others are far less noticeable. For example, individuals with absence seizures might suddenly stop what they were doing for less than ~15 seconds before recovering quickly, sometimes not even realizing that they had a seizure at all².

Finally, where the overactivity starts in the brain, and where it spreads is also variable between people. Sometimes there is a single problematic area of the brain that causes the seizures, while other times there is no obvious problematic area². There is still so much we are learning about epilepsy and all of the variability that comes with this disorder. Each step forward of understanding allows for more specific, personalized, and effective treatments than ever before.

What can we do about epilepsy?

In good news, treatment options for epilepsy continue to improve. There are now powerful medications that allow many to live seizure-free. Approximately 70% of epilepsy cases can be well treated through these existing treatments¹. However, access to these medications is not a guarantee, especially for individuals in low-income regions. Additionally, many of these medications have serious side effects which can heavily impact an individual’s quality of life, especially if they need to take the medication for many years. This means that while these medications are powerful tools in a doctor’s medical arsenal, more innovations need to be developed and explored to treat all individuals and minimize harmful side effects. 

Some alternate paths to treat epilepsy that researchers are exploring is the use of Cannabidiol (CBD)³, or modifications of diet⁴ . Another particularly science-fiction sounding treatment is known as “closed loop stimulation⁵” where doctors implant an electrical stimulator and a monitor into an individual’s brain. The monitor then detects when that person is about to have a seizure and stimulates the brain in response. If the brain is stimulated in just the right way, it may be possible to halt the seizure before it really starts. If seizures are wildfires, closed loop stimulation aims to be a fire alarm/sprinkler. 

Finally, when all other treatment options fail, doctors turn to surgical intervention. In some cases where there is a clear problematic area of the brain that is consistently starting seizures, doctors will consider surgically removing that section of the brain. Removing part of someone’s brain is as big of a deal as it sounds. During these brain surgeries, the patients are often kept awake. While this may sound like something out of a nightmare, it is very important. The surgeons want to remove the areas of the brain causing seizures, but not anything that is important for the patient’s ability to live their typical life. For example, one of the common starting places for seizures is very near areas of the brain associated with language. By carefully testing this area during the surgery, the surgeon can make sure that when they remove brain tissue, that they are not going to impair the patient’s ability to speak or understand language. This precaution is only possible by having a conversation with the patient during the surgery. Fortunately, because there are no pain sensors in the brain, this is not painful for the patients. Part of the reason for this caution is unfortunately the result of learning from past mistakes. In the pursuit of best patient care, some past surgical treatments have led to unintended consequences. 

Lessons learned along the way

A hallmark of modern medicine is attempting to provide the best treatment possible with the state of scientific understanding of the time, and learning from mistakes. Some of the surgeries performed in the past to treat epilepsy, while effective at reducing seizures, also caused profound changes and impairments to the individual’s behaviors and abilities. One of the more famous examples is that of Henry Molaison (aka H.M.)⁶ who had part of his brain removed in 1953 as a treatment for epilepsy⁶. Henry indeed had a large reduction in seizures, however he was also left with a severe impairment in his ability to create new memories. While the tragic nature of this unexpected side effect cannot be overstated, H.M. became one of, if not the most influential research participant in the history of neuroscience. His impairments in memory as a result of specific brain regions being removed gave researchers a clear trail to follow to better understand memory in the brain. 

In a similar vein, the human brain has two large symmetrical halves on each side of the body. Each half communicates with the other primarily through a specific connection point. This connection point was at one time considered a promising surgical separation point for people with epilepsy. If one half of the brain begins to have a seizure, and the connection to the other half has been severed, the effect of the seizure will be reduced. If seizures are wildfires, separating the halves is creating a fire break. Severing the two halves of the brain led to unintended consequences, which in turn, have helped to shape how the two halves of the brain are understood today.

Finally, during the safe, modern surgeries that we discussed above, many individuals with epilepsy have volunteered to participate in research experiments on a huge number of topics. These experiments pose minimal additional risk to the patient during surgery, but allow for direct monitoring of the activity of brain cells which is something that is rarely possible in humans outside of opportunities where an individual is already having a brain surgery. These volunteers have  contributed heavily towards better understanding of the brain in a multitude of ways. 

Looking forward

Epilepsy is simultaneously one of the most straightforward classes of brain disorders, while also being incredibly challenging to treat because of how many ways that it can be caused and express itself in patients. While research and medicine has come a long way, the continued study of epilepsy is still critical to help the millions affected. In addition, study and treatment of epilepsy has led to large strides in understanding the brain in ways far removed from seizures. Who knows what other insights into the brain’s function have yet to reveal themselves along the way. 

References

1. World Health Organization. (2024, February 7). Epilepsy [Fact sheet]. World Health Organization. https://www.who.int/news-room/fact-sheets/detail/epilepsy
2. Epilepsy Foundation. https://www.epilepsy.com. Accessed October 8, 2024.
3. Ali, S., Scheffer, I. E., & Sadleir, L. G. (2019). Efficacy of cannabinoids in paediatric epilepsy. Developmental Medicine & Child Neurology, 61(1), 13–18.
4. Ketogenic Diet. Epilepsy Foundation https://www.epilepsy.com/treatment/dietary-therapies/ketogenic-diet.
5. Sisterson ND, Wozny TA, Kokkinos V, Constantino A, Richardson RM. Closed-Loop Brain Stimulation for Drug-Resistant Epilepsy: Towards an Evidence-Based Approach to Personalized Medicine. Neurotherapeutics. 2019;16(1):119-127. doi:10.1007/s13311-018-00682-4
6. Squire LR. The legacy of patient H.M. for neuroscience. Neuron. 2009;61(1):6-9. doi:10.1016/j.neuron.2008.12.023

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