Posttraumatic epilepsy (PTE) is a recurrent seizure disorder that apparently results from injury to the brain.[1] This injury may be due to multiple types of head insults often labled traumatic brain injury (TBI). There is an increase in PTE due to increasing TBI.[2]
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. The former definition of epilepsy required 2 unprovoked seizures, but the updated definition of epilepsy can be met with 1 unprovoked seizure and high likelihood of another. This blurrs the definition of PTS and PTE, but it is important to differentiate between the two. As PTS is a provoked seizure it is different than unprovoked seizure, but late PTS may be hard to differentiate from PTE.
In a patient who had a seizure 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.
The mechanism by which trauma to brain tissue leads to recurrent seizures is unknown because there are so many different types of head insults and the excitatory cascade is a series of complex processes. Cortical lesions with cortical dysfunction 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.
New information suggests that inflammation and immune system alteration may be contributing to the development of seizures and epilepsy. The TBI that leads to PTE in humans is probably the best model for studying epileptogenesis, but even then it is difficult to do so. This offers an opportunity to intervene with therapry to decrease the developement of PTE.
By definition, PTE is a result of injury to the brain. Patient factors that increase susceptibility to PTE include the following[3] :
Apolipoprotein E epsilon4 genotype has been proposed as a risk factor,[4, 5] but other studies have not found that to be the case.[6, 7]
Injury-related factors that increase the risk of PTE are as follows[8] :
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 and is higher in the military due to higher-velocity projectiles. 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.[3, 4]
The incidence of PTS is as high as 50% in military series, as these studies include many patients with penetrating head injuries.[10] 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.[11]
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.
As in any seizure disorder with alteration of awarness, patients must be warned to exercise caution during bathing (showers are safer), swimming, and climbing heights. They should never be alone during these activities. Other practical issues come into play such as cooking with open flame, operating dangerous equipment, and so on. 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.
Posttraumatic seizures (PTS) are usually partial (focal) or secondarily generalized tonic-clonic (bilateral tonic clonic). Often, if only the secondarily generalized seizure is reported, one can assume there was a focal onset of PTS. Most early PTS are partial seizures, whereas most late PTS, especially when in patients with posttraumatic epilepsy (PTE), are partial-onset with and without secondarily generalized seizures.
There are no specific findings noted on physical examination in some patients, but others may have some findings depending on the location and severity of the TBI, including focal deficits such as language problems, or even diffuse psychomotor slowing.
Posttraumatic status epilepticus is a complication of PTE. It is more common in children than in adults.
Psychological problems related to social isolation and the stigma of epilepsy are common in PTE. There could be personality changes as well as a number of problems such as posttraumatic stress disorder (PTSD), anxiety, and depression.
With TBI, many patients may have posttraumatic headaches and some could develop migraines. Should they be complex, sometimes the symptoms overlap with seizures.
If the PTE is severe with frequent secondarily generalized seizures then the risk of sudden unexpected death in epilepsy (SUDEP) is increased.
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. If the patient is otherwise in stable condition, the serum electrolytes are within the normal range, and the neurologic findings are the same as those before the seizure, further laboratory studies are not needed.
In a patient presenting some time after the injury, the usual investigations applicable for the first epileptic seizure should be performed. See First Pediatric Seizure and First Adult Seizure for more discussion of these topics. It often includes and EEG and neuroimaging.
Serum prolactin measurement can be measured after the seizure to help differentiate pseudoseizures from seizures. However, this is still more of a research point rather than a well-recognized standard test.
Brain magnetic resonance imaging (MRI) is the study of choice, and many clinicians perform it in all patients with posttraumatic seizures. If MRI is not readily available, head computed tomography (CT) can be substituted. CT is less sensitive than MRI, but should be able to depict all pathology (eg, intracranial bleed) that needs urgent intervention.
Electroencephalography (EEG) is useful mainly for localizing seizure foci and for prognosticating their severity. EEG is not helpful in predicting the likelihood of posttraumatic seizure in a given patient. However, it may be helpful in predicting relapse before anticonvulsant medication is withdrawn.
Video-EEG monitoring may be helpful in differentiating between pseudoseizures and posttraumatic epilepsy seizures. The video-EEG monitoring should be performed on those who are medically refractory to pursue epilepsy resective surgery or neurostimulation.
Early posttraumatic seizure (PTS) should be treated promptly, as seizure activity is likely to further damage the already-compromised brain. For active seizures, IV phenytoin and sodium valproate are the antiepileptic drugs (AEDs) of choice and are usually effective in stopping the seizure, along with IV benzodiazepine.[13]
With late PTS, treatment is not mandatory.[13] Some patients isolated of seizure may choose not to take regular medication; in any case, compliance with long-term treatment is often poor in this group of patients. With PTE, patients should be on seizure medications. Surgical treatment is an option for PTE refractory to medication.
Treatment of posttraumatic epilepsy (PTE) does not require hospitalization. Admission may be needed for the treatment of status epilepticus or for video-EEG telemetry to assist in the diagnosis.
Go to Epilepsy and Seizures for an overview of this topic.
Any anticonvulsant, except ethosuximide can be prescribed for PTE. To the authors' knowledge, no randomized controlled studies have been performed to prove that one AED is better than another in PTE. Some authors also recommend phenytoin,[14] but it seems to increase the risk of impairing cognitive function. Newer AEDS—particularly, topiramate and levetiracetam—are showing promise in this regard.[15, 16] . An AED that also may be useful for some of the symptoms of TBI such as headaches, anxiety can be taken into consideration when selecting AED.
Go to Antiepileptic Drugs for complete information on this topic.
Surgical treatment of PTE, as in other types of epilepsy, has the goal of excision of the epileptogenic focus. Precise identification and excision of the focus is can be more difficult in PTE in other types of epilepsy, depending on the severity and location of TBI.
Go to Epilepsy Surgery for complete information on this topic.
Prevention of PTE starts with prevention of head trauma. Clinicians should encourage preventive strategies, such as use of child seats and the use of helmets when cycling. Sports head injury guidlines should be followed to prevent recurrent head injury.
A guideline from the American Academy of Neurology notes that in adult patients with severe traumatic brain injury, prophylaxis with phenytoin is effective in decreasing the risk of early PTS; however, AED prophylaxis is probably not effective in decreasing the risk of late PTS (ie, PTS occurring beyond 7 days after injury).[17] Long-term AED treatment should be considered only after a diagnosis of PTE has been made.[18]
Similarly, a 2001 Cochrane Review concluded that although prophylactic use of AEDs soon after head injury reduces early seizures, there is no evidence that it reduces late seizures or has any effect on death or neurological disability.[19]
A study of seizure prophylaxis in patients with severe traumatic brain injury or subarachnoid hemorrhage found that intravenous levetiracetam appeared to be an alternative to fosphenytoin in that setting.[20] Ongoing clinical trials are addressing the antiepileptogenic potential of topiramate and levetiracetam in patients with traumatic brain injury.[15]
Administration of AEDs for the first week after neurosurgery is a routine practice.[21] Phenytoin has most often been used for this purpose, but levetiracetam is gaining popularity; it appears to be as effective, with fewer adverse effects.[22]
Some have proposed the existence of a window of opportunity of about 1 hour after traumatic brain injury. During this period, treatment with an AED (eg, sodium valproate) may prevent or abort the epileptogenic process.[23] Studies to explore such treatment are under way.
Some natural antioxidants, such as alpha-tocopherol and condensed tannins, have been demonstrated to be prophylactic for the occurrence of epileptic discharge in the iron-injected animal brain.[24]
Consult a neurologist to confirm the diagnosis. Consult with a psychiatrist if patient has nonepileptic seizures. Consultation with an epileptologist and neuropsychologist should be a part of the workup if surgery is considered.
Regular follow-up should be performed for a review of seizure frequency and medications; for neuropsychological assessment; and for monitoring of adverse effects, drug levels if indicated, and the patient's neurologic status.
The Vietnam Head Injury Study (VHIS) followed more than 1,200 Vietnam veterans over a 30-year period who sustained mostly penetrating head injuries. The VHIS concluded that patients with penetrating head injuries carry a high risk of PTE decades after their injury. Predictors of PTE include lesion location (particularly if the location includes the left parietal lobe), lesion size, lesion type, and retained ferric metal fragments. Those patients will require long-term medical follow-up.[10]
Early posttraumatic seizure (PTS) is treated with various antiepileptic drugs (AEDs). In most cases, administering the medication via the intravenous (IV) route is desirable, as the patient is still in the recovery stage from the head injury; phenytoin or fosphenytoin is the drug of choice for IV administration for acute seizures.
No evidence suggests that antiepileptic drugs (AEDs) influence the incidence of late PTS; therefore, prophylaxis has no place in caring for patients with head injuries. However, AEDs are effective in patients who develop posttraumatic epilepsy (PTE). The main drugs used for PTE are valproate and carbamazepine.
Also see Antiepileptic Drugs.
Clinical Context: Valproate is chemically unrelated to other antiseizure drugs. Its mechanism of action has not been established; it may be related to increased brain levels of gamma-aminobutyric acid (GABA) or to enhanced GABA action. Valproate may potentiate postsynaptic GABA responses, affect the potassium channel, or have a direct membrane-stabilizing effect.
For conversion to monotherapy, the concomitant AED dose is ordinarily reduced by about 25% every 2 weeks. Reduction may start with therapy or delayed 1-2 weeks if seizures are possible with reduction; closely monitor patients during this time for increased seizure frequency.
As adjunctive therapy, valproate may be added to the regimen at 10-15 mg/kg/d. The dosage may increase by 5-10 mg/kg/wk for optimal clinical response. Optimal clinical response is usually achieved at a dose of less than 60 mg/kg/d.
Clinical Context: Carbamazepine is indicated for complex partial seizures. It may block posttetanic potentiation by reducing summation of temporal stimulation. After therapeutic response, the dose can be reduced to the minimum effective level, or discontinued at least once every 3 months.
Clinical Context: Phenytoin may act in the motor cortex, inhibiting spread of seizure activity; it may inhibit activity of brainstem centers responsible for the tonic phase of grand mal seizures.
Dosages must be individualized. Administer a larger dose before sleep if the dose cannot be divided equally. To minimize GI irritation, administer with or immediately after meals. Rapid injection or direct IV injection may cause severe hypotension or CNS depression.
Clinical Context: Topiramate is a sulfamate-substituted monosaccharide with a broad spectrum of antiepileptic activity that may have state-dependent sodium channel blocking action, potentiating the inhibitory activity of the neurotransmitter gamma-aminobutyrate (GABA). It may block glutamate activity.
Clinical Context: Levetiracetam is used as adjunctive therapy for partial seizures and myoclonic seizures. It is also indicated for primary generalized tonic-clonic seizures. Its mechanism of action is unknown.
These agents prevent seizure recurrence and terminate clinical and electrical seizure activity.