Traumatic brain injury has long been associated with an increased risk of epilepsy, but the importance of repeated injuries has not been systematically investigated. Researchers have now analysed registry data from 2.5 million individuals born in Denmark and found that the risk of developing epilepsy doubles after the first traumatic brain injury and is 4.5 times higher after the second injury. The risk remains increased for decades after traumatic brain injury. The researchers hope the new knowledge can help to prevent epilepsy from developing after such injury.
Traumatic brain injury is a major global public health problem, with more than 69 million people affected annually. Although the possible adverse consequences of a brain injury increase with its severity, studies suggest that even mild injury can have long-term consequences for the function of the nervous system. Accordingly, the risk of developing epilepsy increases after traumatic brain injury – especially shortly afterwards. A new study examined the short- and long-term associations between epilepsy and the number and severity of traumatic brain injuries.
“Of the 2.5 million people studied, 37,200 developed epilepsy during follow-up. Those with a traumatic brain injury had twice the risk of developing epilepsy, and this risk again doubled for those who sustained a second injury. Women were more likely than men to develop epilepsy after mild injury. In contrast, men were more likely than women to develop epilepsy after severe injury. Although the absolute risk was low, and people who experience such injury should not be apprehensive for the rest of their lives, they should be aware of the symptoms of epilepsy and seek treatment if they experience such signs,” explains the first author, Kasper Lolk, Department of Clinical Medicine, Aarhus University.
Doubled and doubled again
Epilepsy is a group of diseases characterized by a brain malfunction that can have several different causes and forms ranging from momentary memory lapses to convulsive seizures and loss of consciousness. Although some people are born with an imbalance in the connections of the brain that leads to epilepsy, traumatic brain injury is a leading cause of acquired epilepsy later in life.
“Although severe brain injury can be identified by brain imaging, the injury from mild head trauma (concussions) cannot be detected this way. Nevertheless, individuals may have symptoms long after the injury, and epilepsy is known to be one of the most frequent and severe manifestations of brain injury. We wanted to determine whether the risk of epilepsy increases after repeated traumatic brain injuries and whether factors including age, sex and the interval between the injuries were associated with the risk of developing epilepsy,” says Kasper Lolk.
Indeed, several types of symptoms from the nervous system have previously been observed among people who have had several traumatic brain injuries, and the theory is therefore that these injuries might lower the convulsive threshold for seizures and in turn render people more susceptible to seizures following new injuries.
“The association we discovered was very convincing. The overall risk doubled following the first traumatic brain injury and more than doubled again with subsequent injuries. Further, the hazard ratio increased with the severity of the first and second injuries – especially after severe injury,” explains Kasper Lolk.
Important information for prevention
The study also showed that women were more likely than men to develop epilepsy after mild injury. In contrast, men were more likely than women to develop epilepsy after severe injury.
“The difference may result from different injury mechanisms, such as the force of injury for men versus women. Physiological characteristics such as skull and brain shape, neck strength and hormonal influences may also affect the risk of seizures after brain injury. Another possibility is that societal pressure may cause men to underreport symptoms, which may distort the numbers,” explains Kasper Lolk.
The fact that men seem to develop epilepsy more frequently than women following traumatic brain injury is very important information for prevention, since men account for three fourths of the severe brain injuries. Although severe brain injuries likely have greater implications for the individuals affected, in a societal perspective, the possible effects of mild injuries may be more important since they account for about 75% of all such injuries.
“Several years may elapse between traumatic brain injury and the first seizure. Our study shows that the risk was increased for at least 20 years after injury, but we do not yet know why. One theory is that the injured area in the brain causes inflammation. This natural response should help to heal the damage, but the immune response may also damage the brain tissue, resulting in the development of epilepsy,” says co-author Jakob Christensen, Clinical Associate Professor, Department of Clinical Medicine, Aarhus University.
Relax and recover
Further research is needed to clarify the underlying mechanisms behind the development of epilepsy and to identify potential ways to prevent epilepsy from developing following traumatic brain injury. However, no treatment strategy has yet been identified.
“Something happens during these 10–20 years after injury that we want to learn to influence so that we can potentially prevent the development of epilepsy after traumatic brain injury. Attempts have been made to slow the development of epilepsy using anticonvulsants, but to no avail. We think that the 90–95% of people who do not develop epilepsy may provide part of the answer. What makes these people protected from developing epilepsy, and can these protective mechanisms be copied?” says Jakob Christensen.
While the reasons are being clarified and possible prevention methods and treatment developed, the main result of the study is to raise awareness of the increased risk of epilepsy following repeated traumatic brain injuries.
“You cannot overprotect yourself for the rest of your life. Athletes, for example, can receive violent blows to the head as part of sports activities. When this happens, it is important to take time to rest and ensure that the brain has the opportunity to recover from the injury,” concludes Jakob Christensen.