Radiosurgery or Open Surgery for Epilepsy Trial
Radiosurgery or Open Surgery for Epilepsy Trial
This study will compare radiosurgery (focused radiation, Gamma Knife Radiosurgery) with
 temporal lobectomy (standard surgical care) as a treatment of temporal lobe epilepsy.
 Patients who have seizures that begin in their temporal lobe that are not controlled with
 medications into the trial will be offered entry. Patients with a high likelihood of having
 their seizures controlled with open surgery will have treatment randomized between the
 standard surgery and radiosurgery. A prior study has shown that focused radiation
 (radiosurgery) may also reduce or eliminate seizures arising from the temporal lobe. The main
 study hypothesis is that radiosurgery is as safe and effective as temporal lobectomy in
 treating patients with seizures arising from the medial temporal lobe.
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.