This is Where in the Brain Epilepsy Comes From
“Now we know more about what brain circuits may play a role in both the cause and control of epilepsy.”
A recent study conducted by researchers from the Brigham and Women’s Hospital has shed light on focal epilepsy, a condition affecting more than 30 million individuals worldwide. This type of epilepsy is commonly linked to brain lesions, such as those caused by stroke.
However, the reasons why certain lesion locations result in epilepsy while others do not have remained unclear. The investigators utilized a technique called lesion network mapping to uncover a common brain circuit that may connect different lesion locations and contribute to the development of epilepsy.
Their findings, published in JAMA Neurology, provide valuable insights into potential targets for brain stimulation.
Lead author Dr. Frederic Schaper, an Instructor of Neurology at Harvard Medical School and a scientist at the Brigham and Women’s Center for Brain Circuit Therapeutics, highlighted the significance of understanding the origins of epilepsy and the brain circuits that require modulation for effective treatment. By employing a wiring diagram of the human brain, lesion network mapping allowed the researchers to move beyond individual lesion locations and map the associated brain circuitry.
The team examined five datasets comprising over 1,500 patients with brain lesions. The participating centers included renowned institutions such as the Brigham and Women’s Hospital, Massachusetts General Hospital, Boston Children’s Hospital, Northwestern University, and University Hospitals of Turku in Finland, Maastricht in the Netherlands, and Barcelona in Spain. Various types of brain lesions, including stroke, trauma, and tumors, were studied to identify common network connections associated with epilepsy across different regions and types of brain damage.
One of the datasets focused on combat veterans from the Vietnam Head Injury Study, initiated in the 1960s due to an increased incidence of epilepsy resulting from combat-related brain injuries caused by shrapnel wounds.
Dr. Jordan Grafman, a co-author from the Shirley Ryan AbilityLab in Chicago, noted, “In our studies, up to 50 percent of Vietnam combat veterans suffered at least one seizure post-injury, sometimes many years after the injury. However, it has remained unclear why lesions to some locations cause epilepsy and others don’t.”
The researchers at Brigham compared the locations of brain damage in patients who developed epilepsy with those who did not. They discovered that lesions associated with epilepsy were dispersed throughout the brain. Importantly, these lesion locations were connected to a common brain network, suggesting that the disrupted brain connections, rather than the lesion locations themselves, played a crucial role in epilepsy development.
These findings hold potential clinical implications for predicting the risk of epilepsy following brain damage.
Dr. Schaper emphasized that if a lesion could be mapped to the identified brain network, it might be possible to estimate an individual’s likelihood of developing epilepsy after a stroke. Although this is not yet a clinical tool, the study lays the groundwork for future investigations into the use of human brain networks to predict epilepsy risk.
The key brain connections identified by the researchers were located deep within the brain, specifically in regions called the basal ganglia and cerebellum, rather than on the brain’s surface. These deep brain structures have long been recognized to modulate and control seizures in animal models of epilepsy and are hypothesized to function as a brain “brake.”
Building on these findings, the researchers analyzed outcome data from 30 patients with drug-resistant epilepsy who underwent deep brain stimulation (DBS) as a treatment for their seizures. The results indicated that patients experienced better outcomes when the DBS site was connected to the same brain network identified through the analysis of brain lesions.
Senior author Dr. Michael Fox, an Associate Professor of Neurology at Harvard Medical School and the founding director of the Brigham and Women’s Center for Brain Circuit Therapeutics, highlighted, “When programming a DBS electrode to improve seizures, it’s hard to know which spot to stimulate because it can take months before the patient’s seizures improve. Identifying this brain circuit for epilepsy may help us target the right spot to improve patient outcomes.”
The authors acknowledge that their study was a retrospective analysis utilizing existing datasets and a wiring diagram of healthy individuals. Future studies could potentially employ patients’ wiring diagrams and prospectively investigate the clinical utility of this circuit as a tool for epilepsy treatment.
“Now we know more about what brain circuits may play a role in both the cause and control of epilepsy, this opens up promising opportunities to guide our therapies” added Schaper. “Future clinical trials are needed to determine if this circuit can effectively guide brain stimulation treatment for epilepsy and benefit patients”.
Source: 10.1001/jamaneurol.2023.1988
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