Transcranial Magnetic Stimulation for Epilepsy
Transcranial Magnetic Stimulation for Epilepsy
The goal of the present clinical trial is to determine whether low frequency (0.5 Hz) rTMS
 can induce long term depression in epileptogenic cortex and thus suppress cortical
 excitability at the epileptic focus.
Investigators propose a safety and feasibility trial for treating epilepsy (Transcranial
 Magnetic Stimulation for Epilepsy. Principal Investigator: Robert Fisher, MD, PhD, Stanford
 University). In this approach, the cortical source of epileptic discharges is first localized
 with dense array electroencephalography (256-channel dEEG). This localization is then
 registered with neuronavigator software to allow precise targeting with slow (0. 5 Hz)
 repetitive Transcranial Magnetic Stimulation (rTMS) with the STM9000. The purpose in the
 feasibility study is to introduce Long Term Depression (LTD) of the seizure onset zone in
 order to reduce epileptiform discharges. The goal in the future pivotal trial will be to
 extend this approach to suppress seizures. The funds for this trial are provided by Stanford
 University. A loan of dEEG equipment and consulting are provided by Electrical Geodesics,
 Inc. (EGI). EGI seeks FDA's approval for this trial. EGI is the manufacturer of the dEEG
 system (GES 400) and the US distributor of the EB Neuro STM9000 rTMS system (manufactured in
 Italy by EB Neuro, S.p.A.).

 The eventual goal will be a pivotal trial for a de novo 510k for dEEG-guided rTMS for
 suppressing epileptic seizures. The more limited goal of suppressing epileptic discharges
 (spikes) will allow careful evaluation of safety while demonstrating feasibility of the
 therapeutic action. In preparing this request, the investigators have studied the guidance on
 the special controls described for rTMS in the FDA Class II Special Controls Guidance
 Document: Repetitive Transcranial Magnetic Stimulation (rTMS) Systems, Document issued on:
 July 26, 2011. In addition, because patients with epilepsy are at particular risk of seizures
 that may be induced or exacerbated by rTMS, investigators also address the unique risks of
 this population, the existing evidence on safety and efficacy of rTMS treatment of the
 epileptic focus, and the mitigation the investigators propose to minimize the risks.

 EGI has received an IDE for a safety and feasibility trial for treating epileptic discharges
 with a different method and device, the Geodesic Transcranial Electrical Neuromodulation
 (GTEN 100) system. The primary difference in the present proposal is the use of rTMS (instead
 of the GTEN 100) to induce long term depression and thus suppression of the cortical
 excitability at the epileptic focus. Dr. Robert Fisher, the Principal Investigator on this
 project, is EGI's unpaid consultant. Dr. Fisher has received an IRB approval at Stanford
 University Hospital for the larger study with this title for 10 patients with dEEG-guided
 rTMS treatment of focal epilepsy with the GES 400 and STM9000. The present trial is a safety
 and feasibility study with 10 patients that will be conducted with an informed consent form
 that is now specific to this safety and feasibility study.
Inclusion Criteria:

 1. Failure of adequate seizure control with prior use of at least 2 anti-seizure drugs.

 2. at least one clearly identified and localizable likely seizure onset focus, as defined
 by the discharges (typically epileptiform spikes) and as identified by dEEG assessment
 through one or more routine clinical dEEG evaluations. This focus must be 2 to 3 cm
 from the head surface (to be reachable by TMS). Where multiple spike foci are present
 and meet these criteria, then the focus with either clinically relevant symptoms or
 the most spikes (or both) will be chosen as the target for treatment.

 3. two or more partial seizures, with or without secondary generalization, in the last
 month, but less than 10 seizures per day.

 4. Anti-seizure drug regimen has remained unchanged for the month before study entry, and
 there is reasonable likelihood of stability for the duration of the study, with the
 exception of allowing short-term rescue medications, such as lorazepam.

 5. a history of epilepsy for at least 2 years.

 6. age of 22 years and older.

 Exclusion Criteria:

 1. If of childbearing potential, the patient must agree to use an effective method of
 birth control during the study and cease participation if pregnant.

 2. Nursing mothers are excluded.

 3. A history or condition of progressive brain disorders, serious systemic diseases,
 symptomatic cerebrovascular disease, cardiac disease, or alcohol abuse. Special
 conditions, for example, non-malignant brain tumors and vascular malformations, can be
 considered for entry on a case-by-case basis. Patients are not excluded on the basis
 of previous psychiatric hospitalizations or suicide attempts.

 4. A history or condition of (generalized) status epilepticus or psychogenic seizures.

 5. Presence of a cardiac pacemaker, vagus nerve stimulator, or metal implantation in the
 body (other than the teeth) including neurostimulators, cochlear implants, and
 implanted medication pumps.

 6. Previous surgery involving opening the skull.

 7. Unable to express presence of pain or discomfort.