Preventing Epilepsy After Traumatic Brain Injury With Topiramate

Traumatic brain injury (TBI) causes epilepsy in up to 30% of civilian and 50% of military
head injuries, exacerbating chronic neurological disability. There is currently no method
for preventing epilepsy after TBI. We hypothesize that the new antiepileptic drug,
topiramate (TPM), will (1) reduce acute seizures and prevent the development of epilepsy
following TBI and (2) improve neurological recovery. We propose to perform a pilot clinical
trial to develop the necessary infrastructure for larger scale randomized clinical trials to
test TPM, and, possibly, other new antiepileptic drugs with neuroprotective properties, for
their ability to prevent epilepsy after TBI. Subjects with TBI will be randomized within 24
hours to one of three groups: 1) TPM for one week, 2) TPM for three months, or 3) phenytoin
for one week. Subjects will be followed for two years for the development of seizures and
for neurological outcome. Serial EEGs and MRIs will be performed to explore potential
mechanisms for the development of epilepsy after TBI. These new tools for the clinical study
of epilepsy prevention, and neuroprotection in general, will be developed that can be
applied to a wide variety of studies and which will facilitate future research in this
critical area.

Inclusion Criteria:

1. Moderate to severe traumatic brain injury, defined as one or more of the following:
penetrating head wound seizure within the first hour after injury intracerebral
hematoma or cortical contusion subdural or epidural hematoma Glasgow Coma Score <= 12
or motor score 1-5 (if intubated). Patients who have been pharmacologically paralyzed
will be evaluated after the paralytic has worn off or been pharmacologically reversed
depressed skull fracture requirement for emergent neurosurgical procedure

2. Time since TBI less than 24 hours

3. Age greater than or equal to 18 years

4. Subject capable of giving informed consent or have an acceptable surrogate capable of
giving consent on the subject's behalf. -

Exclusion Criteria:

1. Known prior history of epilepsy or unprovoked seizures. Patients with a history of
acute symptomatic seizures (e.g. febrile seizure, alcohol withdrawal seizure) will
not be excluded

2. Administration of an antiepileptic drug before enrollment

3. History of allergy to topiramate or phenytoin

4. Pregnancy or breast-feeding. Women of childbearing potential must have a negative
pregnancy test (urine pregnancy test or serum beta-HCG) before randomization

5. Compromised renal function with serum creatinine > 2

6. Severe concurrent illness with life expectancy <6 months

7. Treatment with another investigational agent for TBI

8. Unable to take medications orally and contraindication to placement of nasogastric
tube.

9. Irreversibly fatal TBI

1. All four findings: Glasgow Coma Score = 3, no pupillary reaction, age > 45
years, and severe coagulopathy OR

2. Severe brainstem lesion on neuroimaging studies

10. Patients with a history of kidney stones or glaucoma.

11. Inability to maintain adequate fluid intake while taking topiramate.

12. Patients whose TBI is a result of self inflicted injury

13. Patient's who are currently using illicit drugs -