Background
Posttraumatic epilepsy (PTE) is a recurrent seizure disorder that apparently results from injury to the brain. This injury may be due to head trauma or to an operation on the brain.
PTE must be differentiated from posttraumatic seizures (PTS), which is a broader-spectrum term and signifies seizures that occur as a sequel to brain injury. Seizures that occur within 24 hours after brain injury are called immediate PTS. PTS that occur within 1 week after injury are termed early PTS, and seizures that occur more than 1 week after injury are termed late PTS. About 20% of people who have a single late posttraumatic seizure never have any further seizures, and these people should not be labeled as having PTE.
In a patient who is still hospitalized after a recent head injury, investigation of a seizure should focus on determining whether an intracranial bleed or a change in clinical condition (eg, hyponatremia) has caused the seizure (see Workup). Early PTS should be treated promptly, but treatment for late PTS is not mandatory (see Treatment and Management)
Go to Epilepsy and Seizures for an overview of this topic.
Pathophysiology
The mechanism by which trauma to brain tissue leads to recurrent seizures is unknown. Cortical lesions seem important in the genesis of the epileptic activity. Early seizures are likely to have a different pathogenesis than late seizures; early PTS are thought to be a nonspecific response to the physical insult.
The PTE kindling model of epilepsy postulates that iron deposition from extravasated blood leads to damage by free radicals, and the accumulation of glutamate leads to damage by excitotoxicity. Animal studies suggest that disruption of the blood-brain barrier is likely to contribute to the generation of seizures in PTE.
Etiology
By definition, PTE is a result of injury to the brain. Patient factors that increase susceptibility to PTE include the following[1] :
- Age younger than 5 years or older than 65 years
- Chronic alcoholism
Apolipoprotein E epsilon4 genotype has been proposed as a risk factor,[2, 3] but other studies have not found that to be the case.[4, 5]
Injury-related factors that increase the risk of PTE are as follows[6] :
- Severe trauma
- Penetrating head injuries
- Intracranial hematoma
- Linear or depressed skull fracture
- Hemorrhagic contusion
- Coma lasting more than 24 hours
- Early PTS
- Focal neuroimaging or electroencephalographic abnormalities in the acute postinjury period[7]
Epidemiology
Although the incidence of epilepsy in the general population is estimated at 0.5-2%, the incidence of PTS for all types of head injuries is 2-2.5% in civilian populations. This incidence increases to 5% in hospitalized neurosurgical patients. When only severe head injuries (usually Glasgow Coma Scale score < 9) are considered, the incidence is 10-15% for adults and 30-35% for children.
In the United States, the incidence of brain injury is highest among young adults; this is reflected in the incidence of PTE in the relevant age group. Early PTS are more common in children, while late PTS are more common in older adults.[1, 2]
The incidence of PTS is as high as 50% in military series, as these studies include many patients with penetrating head injuries.[8] The incidence of seizures (excluding early seizures) after uncomplicated mild head injury is the same in the military population as in the general population.
In Japan, approximately 150,000 cases of PTE occur each year; this equals 10% of all hospitalized patients with head injury and 1% of all outpatients with head injury. In a study from Norway, the incidence of PTE in a mixed age group of patients with severe head injuries was 23%, and there was significant correlation with severity of injury and intracranial surgery.[9]
Prognosis
Approximately 80% of first PTS occur within 2 years of the injury. The risk of PTS decreases with time and reaches the normal value for the population at 5 years after the head injury. About half the patients who develop late PTS have 3 or fewer seizures and go into spontaneous remission thereafter.
Patient Education
As in any seizure disorder, patients must be warned to exercise caution during bathing, swimming, and climbing heights. They should never be alone during these activities. In all situations, appropriate steps should be taken to ensure the safety of the person if a seizure occurs. Patients must also be counseled about the limitations in obtaining or retaining a driver's license.
For patient education information, see the Brain and Nervous System Center, as well as Epilepsy.
Frey LC. Epidemiology of posttraumatic epilepsy: a critical review. Epilepsia. 2003;44 Suppl 10:11-7. [Medline].
D'Ambrosio R, Perucca E. Epilepsy after head injury. Curr Opin Neurol. Dec 2004;17(6):731-5. [Medline].
Diaz-Arrastia R, Gong Y, Fair S, Scott KD, Garcia MC, Carlile MC, et al. Increased risk of late posttraumatic seizures associated with inheritance of APOE epsilon4 allele. Arch Neurol. Jun 2003;60(6):818-22. [Medline].
Anderson GD, Temkin NR, Dikmen SS, Diaz-Arrastia R, Machamer JE, Farhrenbruch C. Haptoglobin phenotype and apolipoprotein E polymorphism: relationship to posttraumatic seizures and neuropsychological functioning after traumatic brain injury. Epilepsy Behav. Nov 2009;16(3):501-6. [Medline].
Chamelian L, Reis M, Feinstein A. Six-month recovery from mild to moderate Traumatic Brain Injury: the role of APOE-epsilon4 allele. Brain. Dec 2004;127:2621-8. [Medline].
Annegers JF, Hauser WA, Coan SP, et al. A population-based study of seizures after traumatic brain injuries. N Engl J Med. Jan 1 1998;338(1):20-4. [Medline].
Angeleri F, Majkowski J, Cacchio G, et al. Posttraumatic epilepsy risk factors: one-year prospective study after head injury. Epilepsia. Sep 1999;40(9):1222-30. [Medline].
Raymont V, Salazar AM, Lipsky R, Goldman D, Tasick G, Grafman J. Correlates of posttraumatic epilepsy 35 years following combat brain injury. Neurology. Jul 20 2010;75(3):224-9. [Medline]. [Full Text].
Skandsen T, Ivar Lund T, Fredriksli O, Vik A. Global outcome, productivity and epilepsy 3--8 years after severe head injury. The impact of injury severity. Clin Rehabil. Jul 2008;22(7):653-62. [Medline].
Hudak AM, Trivedi K, Harper CR, Booker K, Caesar RR, Agostini M, et al. Evaluation of seizure-like episodes in survivors of moderate and severe traumatic brain injury. J Head Trauma Rehabil. Jul-Aug 2004;19(4):290-5. [Medline].
Temkin NR, Dikmen SS, Wilensky AJ. A randomized, double-blind study of phenytoin for the prevention of post-traumatic seizures. N Engl J Med. Aug 23 1990;323(8):497-502. [Medline].
Löscher W, Brandt C. Prevention or modification of epileptogenesis after brain insults: experimental approaches and translational research. Pharmacol Rev. Dec 2010;62(4):668-700. [Medline]. [Full Text].
[Guideline] Chang BS, Lowenstein DH. Practice parameter: antiepileptic drug prophylaxis in severe traumatic brain injury: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. Jan 14 2003;60(1):10-6. [Medline].
Beghi E. Overview of studies to prevent posttraumatic epilepsy. Epilepsia. 2003;44 Suppl 10:21-6. [Medline].
Schierhout G, Roberts I. Anti-epileptic drugs for preventing seizures following acute traumatic brain injury. Cochrane Database Syst Rev. 2001;CD000173. [Medline].
Szaflarski JP, Sangha KS, Lindsell CJ, Shutter LA. Prospective, randomized, single-blinded comparative trial of intravenous levetiracetam versus phenytoin for seizure prophylaxis. Neurocrit Care. Apr 2010;12(2):165-72. [Medline].
Temkin NR. Prophylactic Anticonvulsants After Neurosurgery. Epilepsy Curr. Jul 2002;2(4):105-107. [Medline].
Milligan TA, Hurwitz S, Bromfield EB. Efficacy and tolerability of levetiracetam versus phenytoin after supratentorial neurosurgery. Neurology. Aug 26 2008;71(9):665-9. [Medline].
Temkin NR, Dikmen SS, Anderson GD, et al. Valproate therapy for prevention of posttraumatic seizures: a randomized trial. J Neurosurg. Oct 1999;91(4):593-600. [Medline].
Mori A, Yokoi I, Noda Y, Willmore LJ. Natural antioxidants may prevent posttraumatic epilepsy: a proposal based on experimental animal studies. Acta Med Okayama. Jun 2004;58(3):111-8. [Medline].

