Transcranial Electrical Neuromodulation for Suppressing Epileptiform Discharges

One third of patients with epilepsy continue to have seizures despite receiving antiepileptic
medication. The application of low frequency repetitive transcranial magnetic stimulation
(rTMS) has shown promise for decreasing the frequency of epileptic seizures in drug
refractory patients. The mechanism of action appears to be induction of long term depression
(LTD) in the targeted cortex by the low frequency (0.5 Hz or 1 every 2 sec) pulses.
Unfortunately, the electrical stimulation induced by available TMS coils is limited to the
most superficial (gyral) regions of cortex, whereas epileptic foci may occur in sulci, and in
deep as well as superficial cortex. The investigators have developed the ability to target
currents to specific regions of cortex by aligning source and sink electrodes with flexible
subsets of a 256 channel geodesic electrode array. A first step is accurate localization of
the likely epileptic focus with 256 channel EEG. Detailed computational models of the
electrical properties of head tissues allow optimization studies to select the best pattern
of source-sink electrodes for that individual's head tissues and epileptic focus. The goal of
the safety and feasibility trial is to test whether one week (5 days) of GTEN treatment can
achieve a similar depression of the target cortical region as low frequency rTMS, with the
decrease in excitability measured by suppression of epileptic spikes. This safety and
feasibility trial has received an Investigational Device Exemption from the FDA for treating
20 patients with focal neocortical epilepsy. Pulsed (emulating rTMS) current sequences will
be evaluated. The GTEN system implements a number of advanced technologies that provide
improved targeting compared to conventional rTMS or tDCS, including electronics for both
pulsed and sustained delivery of current with 256 electrodes; double fault safety circuits;
computational modeling of the electromagnetic properties of the patient's head tissue for
GTEN targeting with medical grade software; a lidocaine electrolyte that minimizes pain of
the pulsed or sustained current with up to 200 µA per electrode (2 mA total); and online
safety monitoring for adverse EEG changes with the 256 dEEG array. Based on FDA feedback to
date, success with these trials will allow us to progress to a pivotal clinical efficacy
trial (with separate funding) to support a de novo 510k approval for GTEN treatment for the
temporary suppression of seizures in patients with drug-resistant epilepsy.

Inclusion Criteria:

1. Age 14 to 60.

2. Partial onset seizures (simple or complex) with failure of adequate seizure control
after prior use of at least 2 anti-seizure drugs at effective doses.

3. Only one clearly identified and localizable extratemporal focus of epileptiform
discharges, as defined the discharges (typically epileptiform spikes) and as
identified by dEEG assessment through one or more routine clinical dEEG evaluations.

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

5. 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.

6. A history of epilepsy for at least 2 years.

Exclusion Criteria:

1. Patient is pregnant or becomes pregnant

2. A history or condition of progressive brain disorders, unstable systemic diseases,
symptomatic cerebrovascular disease, cardiac disease, or alcohol/substance
abuse.Special conditions, for example, non-malignant brain tumors and vascular
malformations, can be considered for entry on a case-by-case basis.

3. A history or condition of status epilepticus or psychogenic seizures (seizures not
confirmed by EEG).

4. Presence of a cardiac pacemaker, vagus nerve stimulator, or metal implants in the body
(other than the teeth) including neurostimulators, cochlear implants, and implanted
medication pumps (screened using the LCNI Safety Screening Questionaire).

5. Previous surgery involving opening the skull.

6. Allergy to or condition contraindicating lidocaine.

7. Unable to express presence of pain or discomfort.

8. Allergy to silver

9. Participating in other competing clinical trials

10. Unable to speak English

11. Unable to knowingly give consent