Post-traumatic epilepsy
Post-traumatic epilepsy is a form of acquired epilepsy that results from brain damage caused by physical trauma to the brain. A person with PTE experiences repeated post-traumatic seizures more than a week after the initial injury. PTE is estimated to constitute 5% of all cases of epilepsy and over 20% of cases of acquired epilepsy.
It is not known who will develop epilepsy after TBI and who will not. However, the likelihood that a person will develop PTE is influenced by the severity and type of injury; for example penetrating injuries and those that involve bleeding within the brain confer a higher risk. The onset of PTE can occur within a short time of the physical trauma that causes it, or months or years after. People with head trauma may remain at a higher risk for post-traumatic seizures than the general population even decades after the injury. PTE may be caused by several biochemical processes that occur in the brain after trauma, including overexcitation of brain cells and damage to brain tissues by free radicals.
Diagnostic measures include electroencephalography and brain imaging techniques such as magnetic resonance imaging, but these are not totally reliable. Antiepileptic drugs do not prevent the development of PTE after head injury, but may be used to treat the condition if it does occur. When medication does not work to control the seizures, surgery may be needed. Modern surgical techniques for PTE have their roots in the 19th century, but trepanation may have been used for the condition in ancient cultures.
Classification
Seizures may occur after traumatic brain injury; these are known as post-traumatic seizures. However, not everyone who has post-traumatic seizures will continue to have post-traumatic epilepsy, because the latter is a chronic condition. However, the terms PTS and PTE are used interchangeably in medical literature. Seizures due to post-traumatic epilepsy are differentiated from non-epileptic post-traumatic seizures based on their cause and timing after the trauma.A person with PTE has late seizures, those occurring more than a week after the initial trauma. Late seizures are considered to be unprovoked, while early seizures are thought to result from direct effects of the injury. A provoked seizure is one that results from an exceptional, nonrecurring cause such as the immediate effects of trauma rather than a defect in the brain; it is not an indication of epilepsy. Thus for a diagnosis of PTE, seizures must be unprovoked.
Disagreement exists about whether to define PTE as the occurrence of one or more late, unprovoked seizures, or whether the condition should only be diagnosed in people with two or more. Medical sources usually consider PTE to be present if even one unprovoked seizure occurs, but more recently it has become accepted to restrict the definition of all types of epilepsy to include only conditions in which more than one occur. Requiring more than one seizure for a diagnosis of PTE is more in line with the modern definition of epilepsy, but it eliminates people for whom seizures are controlled by medication after the first seizure.
As with other forms of epilepsy, seizure types in PTE may be partial or generalized. In about a third of cases, people with PTE have partial seizures; these may be simple or complex. In simple partial seizures, level of consciousness is not altered, while in complex partial seizures consciousness is impaired. When generalized seizures occur, they may start out as partial seizures and then spread to become generalized.
Causes
It is not clear why some patients develop PTE while others with very similar injuries do not. However, possible risk factors have been identified, including severity and type of injury, presence of early seizures, and genetic factors.Genetics
may play a role in the risk that a person will develop PTE; people with the ApoE-ε4 allele may be at higher risk for PTE. The haptoglobin Hp2-2 allele may be another genetic risk factor, possibly because it binds hemoglobin poorly and thus allows more iron to escape and damage tissues. However, most studies have found that having family members with epilepsy does not significantly increase the risk of PTS, suggesting that genetics are not a strong risk factor.Severity of trauma
The more severe the brain trauma is, the more likely a person is to have late PTE. Evidence suggests that mild head injuries do not confer an increased risk of developing PTE, while more severe types do. In simple mild TBI, the risk for PTE is about 1.5 times that of the uninjured population. By some estimates, as many as half of individuals with severe brain trauma experience PTE; other estimates place the risk at 5% for all TBI patients and 15–20% for severe TBI. One study found that the 30-year risk of developing PTE was 2.1% for mild TBI, 4.2% for moderate, and 16.7% for severe injuries, as shown in the chart at right.Nature of trauma
The nature of the head trauma also influences the risk of PTE. People who have depressed skull fractures, penetrating head trauma, early PTS, and intracerebral and subdural haematomas due to the TBI are especially likely to have PTE, which occurs in more than 30% of people with any one of these findings. About 50% of patients with penetrating head trauma develop PTE, and missile injuries and loss of brain volume are associated with an especially high likelihood of developing the condition. Injuries that occur in military settings carry higher-than-usual risk for PTE, probably because they more commonly involve penetrating brain injury and brain damage over a more widespread area. Intracranial hematomas, in which blood accumulates inside the skull, are one of the most important risk factors for PTE. Subdural hematoma confers a higher risk of PTE than does epidural hematoma, possibly because it causes more damage to brain tissue. Repeated intracranial surgery confers a high risk for late PTE, possibly because people who need more surgery are more likely to have factors associated with worse brain trauma such as large hematomas or cerebral swelling. In addition, the chances of developing PTE differ by the location of the brain lesion: brain contusion that occurs on in one or the other of the frontal lobes has been found to carry a 20% PTE risk, while a contusion in one of the parietal lobes carries a 19% risk and one in a temporal lobe carries a 16% chance. When contusions occur in both hemispheres, the risk is 26% for the frontal lobes, 66% for the parietal, and 31% for the temporal.Post-traumatic seizures
The risk that a person will develop PTE is heightened but not 100% if PTS occur. Because many of the risk factors for both PTE and early PTS are the same, it is unknown whether the occurrence of PTS is a risk factor in and of itself. However, even independent of other common risk factors, early PTS have been found to increase the risk of PTE to over 25% in most studies. A person who has one late seizure is at even greater risk for having another than one who has early PTS; epilepsy occurs in 80% of people who have a late seizure. Status epilepticus, a continuous seizure or multiple seizures in rapid succession, is especially strongly correlated with the development of PTE; status seizures occur in 6% of all TBIs but are associated with PTE 42% of the time, and quickly halting a status seizure reduces chances of PTE development.Pathophysiology
For unknown reasons, trauma can cause changes in the brain that lead to epilepsy. There are a number of proposed mechanisms by which TBI causes PTE, more than one of which may be present in a given person. In the period between a brain injury and onset of epilepsy, brain cells may form new synapses and axons, undergo apoptosis or necrosis, and experience altered gene expression. In addition, damage to particularly vulnerable areas of the cortex such as the hippocampus may give rise to PTE.Blood that gathers in the brain after an injury may damage brain tissue and thereby cause epilepsy. Products that result from the breakdown of hemoglobin from blood may be toxic to brain tissue. The "iron hypothesis" holds that PTE is due to damage by oxygen free radicals, the formation of which is catalyzed by iron from blood. Animal experiments using rats have shown that epileptic seizures can be produced by injecting iron into the brain. Iron catalyzes the formation of hydroxyl radicals by the Haber–Weiss reaction; such free radicals damage brain cells by peroxidizing lipids in their membranes. The iron from blood also reduces the activity of an enzyme called nitric oxide synthase, another factor thought to contribute to PTE.
After TBI, abnormalities exist in the release of neurotransmitters, chemicals used by brain cells to communicate with each other; these abnormalities may play a role in the development of PTE. TBI may lead to the excessive release of glutamate and other excitatory neurotransmitters. This excessive glutamate release can lead to excitotoxicity, damage to brain cells through overactivation of the biochemical receptors that bind and respond to excitatory neurotransmitters. Overactivation of glutamate receptors damages neurons; for example it leads to the formation of free radicals. Excitotoxicity is a possible factor in the development of PTE; it may lead to the formation of a chronic epileptogenic focus. An epileptic focus is the part of the brain from which epileptic discharges originate.
In addition to chemical changes in cells, structural changes that lead to epilepsy may occur in the brain. Seizures that occur shortly after TBI can reorganize neural networks and cause seizures to occur repeatedly and spontaneously later on. The kindling hypothesis suggests that new neural connections are formed in the brain and cause an increase in excitability. The word kindling is a metaphor: the way the brain's response to stimuli increases over repeated exposures is similar to the way small burning twigs can produce a large fire. This reorganization of neural networks may make them more excitable. Neurons that are in a hyperexcitable state due to trauma may create an epileptic focus in the brain that leads to seizures. In addition, an increase in neurons' excitability may accompany loss of inhibitory neurons that normally serve to reduce the likelihood that other neurons will fire; these changes may also produce PTE.