Radiosurgery or Open Surgery for Epilepsy Trial

The purpose of this study is to compare the effectiveness of Gamma Knife radiosurgery with
temporal lobectomy in the treatment of patients with drug resistant temporal lobe epilepsy.
Aim 1 is designed to compare the seizure-free outcomes and morbidity of radiosurgery for
patients with drug resistant temporal lobe epilepsy with those of open temporal lobectomy.
Our primary hypothesis is that radiosurgery will be non-inferior to lobectomy with respect to
seizure-free rates at 25-36 months following therapy (one-year of seizure freedom beginning 2
years after treatment).

Aim 2 is designed to compare the neuropsychological outcomes in patients undergoing
radiosurgery and temporal lobe surgery, in particular with respect to verbal memory function
for language-dominant hemisphere treated patients. Our hypothesis is that patients treated
for speech-dominant temporal lobe seizures with temporal lobectomy will show greater
reduction in verbal memory than patients treated with radiosurgery.

Aim 3 is designed to determine what changes occur in the quality of life of patients with
temporal lobe epilepsy following radiosurgical treatment as compared with open surgery. Our
primary hypothesis is that there will be improvements (comparing baseline with 3 years
post-treatment) in quality of life measures in both groups. Our secondary hypothesis is that
both open surgery and radiosurgery subjects will undergo transient reductions in quality of
life measures caused by treatment effects during the first year following treatment, but that
quality of life will improve for subjects who become seizure-free, independent of treatment
group.

Aim 4 is designed to compare the cost-effectiveness of radiosurgery compared with open
surgery. Specifically, the marginal cost-utility ratio will fall below $50,000/QALY, a
threshold thought to indicate that outcomes are considered worth the cost.

Inclusion and Exclusion Criteria:

Adults (18 years and older) of either gender who would otherwise be eligible for temporal
lobe resection will be offered enrollment for randomization to RS or ATL.

1. Seizure type: Patients must have simple and/or complex partial seizures with or
without secondary generalization.

2. Seizure Frequency: Patients must have at least 3 complex partial seizures during the 3
month (12 week) baseline seizure diary period with at least 1 of 3 seizures occurring
within the last 2 months (8 weeks).

3. Patients with electrographic evidence of seizures arising from one temporal lobe, with
radiographic evidence of mesial temporal sclerosis in the same temporal lobe will be
included. Patients with normal MRIs, bilateral hippocampal damage, or cortical lesion
will be excluded.

4. Subjects should be on stable doses of antiepileptic medications for at least 3 months
prior to treatment.

5. All female patients of childbearing age will have documented that they are using a
safe and effective means of birth control and will have a negative urine pregnancy
test completed within 1 week prior to their treatment.

6. Patients should be able to understand the potential benefits and risks of this therapy
and be able to understand the protocol and sign their own consent forms. For these
reasons, only patients 18 years and older and with I.Q. greater than or equal to 70
will be included.

7. Patients with any focal neurologic deficit that would make it difficult to detect a
new radiation-associated injury will be excluded. All patients will receive formal
visual field testing (Humphrey) and patients with visual field deficits will be
excluded.

8. Patients with radiographic evidence of other pathologies such as vascular
malformations or tumors will be excluded.

9. Patients with diabetes mellitus or hypertension will be excluded from this study
because radiation injury to the brain is more common in these patients.

10. Subjects should not have significant psychiatric conditions that would make accurate
assessment of seizure frequency difficult, as judged by the principal investigator.
Such conditions include a history of non-epileptic seizures, psychosis (other than
post-ictal psychosis) and severe mood disorders including suicide attempt within past
12 months or noncompliance with psychotropic medications.

11. Patients with a history of significant past or present medical disorders determined
severe enough to prevent participation in a surgical trial by the principal
investigator are excluded.

12. Patients with any progressive neurological disorder (such as multiple sclerosis or
systemic lupus erythematosis) are excluded.

13. Patients with a history of poor compliance with past antiepileptic drug therapy as
judged by the principal investigator are excluded.

14. Patients with a recent history of abusing drugs or alcohol with significance as judged
by the principal investigator are excluded.

15. Patients who are receiving any investigational drugs at the time of enrollment are
excluded.

16. Patients with current use of vigabatrin are excluded. Past use does not exclude a
patient pending a normal formal visual field test.

17. Patients with currently functioning vagal nerve stimulators (VNS) are excluded. Past
use does not exclude a patient as long as the device is explanted. Indwelling VNS
electrodes are permitted in agreement with each center's policies on brain MRI
imaging.

18. Patients who can not be anticipated to participate for the full 36 months of the trial
will be excluded.

19. Native English speakers from the U.S. or other English speaking countries or patients
who learned English before age 5 and were educated in English. Spanish speaking
patients can be included as long as the study site can provide an officially
translated (IRB approved) consent form in Spanish. Non-Spanish speaking patients with
English as a second language (ESL) and/or non-English and non-Spanish speaking
patients can be included only under the following conditions: 1) the study site must
be able to have the consent form translated into the patient's native language using
an official translator, and 2) the study site's neuropsychologist must be willing and
able to assess the patient at baseline and post-treatment at 12, 24, and 36 months in
that patient's native language to ensure the patient's safety.