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emedicine.medscape.com

Posttraumatic Epilepsy
Updated: Dec 06, 2017
Author: David Y Ko, MD; Chief Editor: Selim R Benbadis, MD

Overview

Background
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.

Pathophysiology
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.

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Etiology
By definition, PTE is a result of injury to the brain. Patient factors that increase susceptibility to PTE include the
following[3] :

Age younger than 5 years or older than 65 years

Chronic alcoholism

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] :

Severe trauma

Penetrating head injuries

Intracranial hematoma

Linear or depressed skull fracture

Hemorrhagic contusion

Coma lasting more than 24 hours

Early PTS

History of prior TBI as it tends to be cumulative

Focal neuroimaging or electroencephalographic abnormalities in the acute postinjury period[9]

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 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]

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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 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.

Presentation

History
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.

Physical Examination
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.

Complications

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If the PTE is severe with frequent secondarily generalized seizures then the risk of sudden unexpected death in
epilepsy (SUDEP) is increased.

DDx

Diagnostic Considerations
If a case of posttraumatic epilepsy (PTE) demonstrates atypical features and the seizures continue despite treatment,
consider the possibility of pseudoseizures. Hudak et al found that in patients with refractory PTE following moderate
traumatic brain injury, about 20-30% proved to have psychogenic attacks.[12] This percentage is similar to that in
patients with seizures after nontraumatic brain injury. With severe TBI, some patients have posttraumatic stress
disorder, which can contribute to pseudoseizures.

Therefore, in intractable epilepsy patients, the diagnosis should be verified by video-EEG monitoring, which shows that
the nature of the seizures is psychogenic rather than epileptic. Some frontal lobe seizures may have bizarre features,
so caution should be used if basing the decision solely on clinical features. Video-EEG is very helpful in these patients
for distinguishing true epileptic from nonepileptic seizures; for those with epileptic seizures, it may allow further workup
for epilepsy surgery or vagus nerve stimulation.

Differential Diagnoses
Benign Childhood Epilepsy

Complex Partial Seizures

Confusional States and Acute Memory Disorders

Dizziness, Vertigo, and Imbalance

Frontal Lobe Epilepsy

Generalized Tonic-Clonic Seizures

Head Injury

Neonatal Seizures

Psychogenic Nonepileptic Seizures

Temporal Lobe Epilepsy

Workup

Workup

Approach Considerations
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

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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.

Neuroimaging
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
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.

Treatment

Approach Considerations
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.

Anticonvulsant Therapy
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

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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 Care
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 Posttraumatic Epilepsy

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]

Consultations
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.

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Long-Term Monitoring
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]

Medication

Medication Summary
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.

Anticonvulsants

Class Summary
These agents prevent seizure recurrence and terminate clinical and electrical seizure activity.

Sodium valproate (Depakote, Depakene, Depacon, Stavzor)

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.

Carbamazepine (Tegretol, Carbatrol, Equetro, Epitol)

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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.

Phenytoin (Dilantin, Phenytek)

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.

Topiramate (Topamax)
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.

Levetiracetam (Keppra)
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.

Contributor Information and Disclosures

Author

David Y Ko, MD Associate Professor of Clinical Neurology, Loma Linda University School of Medicine

David Y Ko, MD is a member of the following medical societies: American Academy of Neurology, American Clinical
Neurophysiology Society, American Epilepsy Society

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: SK<br/>Serve(d) as a
speaker or a member of a speakers bureau for: Eisai, Lundbeck, Sunovion, Supernus, UCB.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of
Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Jose E Cavazos, MD, PhD, FAAN, FANA, FACNS, FAES Professor with Tenure, Departments of Neurology,
Neuroscience, and Physiology, Assistant Dean for the MD/PhD Program, Program Director of the Clinical
Neurophysiology Fellowship, University of Texas School of Medicine at San Antonio

Jose E Cavazos, MD, PhD, FAAN, FANA, FACNS, FAES is a member of the following medical societies: American
Academy of Neurology, American Clinical Neurophysiology Society, American Epilepsy Society, American Neurological
Association, Society for Neuroscience

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Brain Sentinel,
consultant.<br/>Stakeholder (<5%), Co-founder for: Brain Sentinel.

Chief Editor

Selim R Benbadis, MD Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and

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Neurosurgery, Tampa General Hospital, University of South Florida Morsani College of Medicine

Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American
Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, American
Medical Association

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Ceribell, Eisai,
Greenwich, Growhealthy, LivaNova, Neuropace, SK biopharmaceuticals, Sunovion<br/>Serve(d) as a speaker or a
member of a speakers bureau for: Eisai, Greenwich, LivaNova, Sunovion<br/>Received research grant from: Cavion,
LivaNova, Greenwich, Sunovion, SK biopharmaceuticals, Takeda, UCB.

Acknowledgements

Nicholas Lorenzo, MD, CPE Chairman and CEO, Neurology Specialists and Consultants; Senior Vice President,
Founding Executive Director, Continuing Medical Education, Gannett Education (Division Gannett Healthcare Group)

Nicholas Lorenzo, MD, CPE is a member of the following medical societies: Alpha Omega Alpha, American Academy
of Neurology, and American College of Physician Executives

Disclosure: Nothing to disclose.

Ewa Posner, MD, MRCP Consultant Pediatrician, Department of Pediatrics, University Hospital of North Durham, UK

Ewa Posner, MD, MRCP is a member of the following medical societies: European Paediatric Neurology Society and
Royal College of Paediatrics and Child Health

Disclosure: Nothing to disclose.

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