A Multicenter Study of Hippocampal Electrical Stimulation (HS, in Mesial Temporal Lobe Epilepsy
A Multicenter Study of Hippocampal Electrical Stimulation (HS, in Mesial Temporal Lobe Epilepsy
The primary goal is to determine whether hippocampal electrical stimulation (HS) is safe and
 more effective than simply implanting an electrode in the hippocampus without electrical
 stimulation (HI), in patients with mesial temporal lobe epilepsy (MTLE). This will be
 assessed by the rate of complex partial seizures per person-month over 6 months of follow-up
 in HS vs. HI. There are two treatment arms: 1) Hippocampal Electrode Implantation with
 Stimulation (HS). 2) Hippocampal Electrode Implantation without stimulation (HI). The
 investigators expect to demonstrate that HS is safe and superior to HI in controlling
 seizures in patients with MTLE.
This is a multicentre, parallel-group, double blind randomized controlled trial involving
 patients with MTLE who may be candidates for resective surgery or whose memory function
 precludes resective surgery. Eligible patients will be randomized in a 2:1 ratio into
 hippocampal electrode implantation with stimulation (HS), or hippocampal electrode
 implantation without stimulation (HI). Patients will be followed for seven months after
 randomization. One month will be devoted to adjustment of interventions, and 6 months to
 follow-up and outcome assessment. At the end of seven months, all patients will be offered
 the option of HS, electrode removal, surgical therapy or medical therapy, based on best
 evidence and patient preference.

 Primary Question: In patients with MTLE, over a 6-month period:

 Is continuous HS plus medical therapy (MT) more efficacious than hippocampal implantation
 (HI) plus MT in reducing seizure frequency?

 Secondary Questions: In patients with MTLE, over a 6-month period:

 1. Is HS safe?

 2. What is the effect of HS on cognition, mood, and quality of life?

 3. What is the effect of HS on psychiatric morbidity?

 4. Is the efficacy of HS associated with the presence, location and amount of interictal
 hippocampal spikes on depth electrode recordings?
Inclusion Criteria:

 -  Unilateral or Bilateral Mesial Temporal lobe Epilepsy.

 -  Age ≥ 18 years.

 -  Global IQ ≥70.

 -  Failure of ≥ 2 AEDs approved for treatment of partial seizures, used alone or in
 combination at recommended dosages.

 -  Average ≥ 3 seizure-days per month in prior 6 months during which disabling seizures
 occurred. Disabling seizures are defined as complex partial seizures with or without
 secondary generalization, or as simple partial seizures that are noticeable by others
 or interfere with function.

 -  Ability to complete self-administered questionnaires.

 -  Availability of reliable collateral historian or witness.

 -  Patient preference for non-resective surgery, or not a candidate for mesial temporal
 resection.

 -  Give written informed consent.

 Exclusion Criteria:

 -  Extratemporal or multifocal epilepsy.

 -  MRI evidence of potentially epileptogenic lesions outside the mesial temporal region.

 -  Lesions precluding electrode implantation (eg, vascular malformations, vascular
 tumors).

 -  Severe hippocampal sclerosis that in the surgeon's opinion precludes accurate
 electrode placement.

 -  Brain lesions that demand prompt surgical therapy (eg, malignant tumors, vascular
 malformations).

 -  Progressive neurological disorders (eg, malignant tumor, dementia, degenerative
 disorders).

 -  Medical or psychiatric conditions precluding surgery or interfering with adherence to
 treatment and follow-up.

 -  Planned pregnancy during the study. Women of child-bearing age will require a negative
 pregnancy test and adequate contraception methods.

 -  Ongoing or planned participation in other studies of new epilepsy therapies.

 -  Contraindication for stereotactic surgery, e.g. bleeding diathesis, anticoagulants,
 treatment with valproate at the time of surgery (risk of bleeding).

 -  Any condition that would make participation in the trial detrimental to the patient's
 health.