Low Frequency Electrical Stimulation of the Fornix in Intractable Mesial Temporal Lobe Epilepsy (MTLE)
Low Frequency Electrical Stimulation of the Fornix in Intractable Mesial Temporal Lobe Epilepsy (MTLE)
The primary aim of the current proposal is to evaluate safety and tolerability, in terms of
 neuropsychological effects of low frequency electrical stimulation of the fornix (LFSF) in
 participants with medically-intractable Mesial Temporal Lobe Epilepsy. Secondary aims include
 evaluation of psychiatric changes, seizure frequency, and quality of life during LFSF.
Low frequency stimulation is an attractive, uninvestigated method for treatment of
 intractable epilepsy. Preliminary animal and human data suggest safety and remarkable
 efficacy of Low frequency stimulation (LFS) in epilepsy. In addition, the duty cycle of LFS
 is very low, implying less electric current injection, with less charge density on the target
 tissue and electrodes, and longer battery life. The current project is a classic
 translational, single-blinded, randomized research project, demonstrating a clear path from
 the laboratory to bedside. If successful, this new therapy will be of great value to patients
 with medically and surgically intractable Mesial Temporal Lobe Epilepsy (MTLE).

 The study is expected to last approximately 5 years, from enrollment of the first patient to
 completion of the final subject, taking into consideration attrition and otherwise-eligible
 subjects who will not elect to participate. Once the study is completed, and enrolled
 participants have completed all required elements of the protocol, a final report will be
 submitted to the FDA. Participants may also discontinue their participation in the study, if
 they wish, at any time.
Inclusion Criteria:

 -  Participants are between the ages of 18 -65 years of age

 -  Participants must have had a non-invasive video-EEG monitoring revealing seizure
 semiology and ictal EEG consistent with unilateral or bilateral MTLE

 -  Participants must have tried and failed two trials of antiepileptic drugs (AEDs)

 -  Participants may have lesional or non lesional hippocampi, as evidenced by brain MRI
 acquired within the previous two years

 -  Participants are prescribed and taking 1-4 AEDs at the time of study entry

 -  Study participants will have intractable (MTLE) with a seizure frequency of at least
 1/month averaged over the preceding 6 months prior to enrollment, including maximum
 seizure-freedom periods of no more than 60 days.

 -  Participants must have a platelet count greater than 125,000 per cubic millimeter and
 prothrombin time (PT) and activated partial thromboplastin time (aPTT) within normal
 limits at the visit prior to surgery

 Exclusion Criteria:

 -  Progressive neurological or medical diseases, such as brain tumors or
 neurodegenerative disease or cancer

 -  Non-compliance with antiepileptic medications as demonstrated by the medical record

 -  Any conditions interfering with electrode implantation

 -  Any non-epileptic seizures

 -  Inability or unwillingness to complete neuropsychological tests or complete seizure
 diaries

 -  Current drug or alcohol use or dependence that, in the opinion of the site
 investigator, would interfere with adherence to study requirements

 -  Pregnant, or planning to become pregnant*

 -  Participation in another research trial where the participant was treated with another
 investigational drug or device within 30 days prior to enrollment of study

 -  Intelligence Quotient showing a general ability Quotient of less than 70. The score
 excludes the contribution of working memory and processing speed (which are areas of
 cognitive functioning that are vulnerable to numerous influences including seizures
 and fatigue and effects of AEDs)

 -  Inability or unwillingness of individual to give written informed consent

 -  Participants who have changes to their antiepileptic medications during the baseline
 phase (as they will need to repeat the baseline phase)

 -  Subjects with history of status epilepticus within the preceding year

 -  History of psychiatric illness necessitating hospitalizations

 -  Subjects who have any of the following implanted devices: aneurysm clips, cardiac
 pacemaker or defibrillator, cochlear implant, spinal cord, DBS, or vagal nerve
 stimulator

 -  Co-morbid conditions that would interfere with study stimulation activities or
 response to treatment, which may include:

 -  Neoplasm with life expectancy < 5 years

 -  Severe chronic pulmonary disease

 -  Local, systemic acute or chronic infectious illness

 -  Life threatening cardiac arrhythmias

 -  Severe collagen vascular disorder

 -  Kidney failure or other major organ system failures