Low Intensity Focused Ultrasound Treatment for Drug-Resistant Epilepsy: An Efficacy Trial

The aim of the proposed pilot study is to investigate patient tolerability and efficacy of
moderate term, repeated exposure of Pulsed Low-Intensity Focused Ultrasound (PLIFUS) in
patients with drug-resistant temporal lobe epilepsy. We hypothesize that the treatments will
be well-tolerated, subjects' EEGs will show improvement (fewer epileptiform discharges), and
that subjects will experience a reduction in seizure frequency as a result of the treatment
without adverse events.

Due to the lack of options for patients with drug-resistant epilepsy, investigations into
alternative noninvasive treatments are warranted. PLIFUS has been shown to safely modulate
neuronal tissue, and is non-invasive and painless. Several human studies have shown that the
use of PLIFUS can suppress somatosensory evoked potentials and induce functional magnetic
resonance imaging (MRI) responses.

Once the subject is enrolled in the study, the subject will be scheduled for a standard brain
MRI scan at BWH if they have not had one in the last 3 months. The subject will be asked to
keep track of their seizure events in the Daily Seizure Log Diary from the screening visit
until 2 months after the last treatment session.

The treatment period will include 8 treatment sessions total. These will occur 2 days per
week for 4 weeks, each lasting approximately 1-2 hours, starting 1 month after seizure
logging begins.

Inclusion Criteria:

- Subjects at least eighteen (18) years of age

- Subjects with drug-resistant temporal lobe epilepsy whose seizures involve altered
awareness (ie failed at least two trials of antiepileptic drugs for seizures), as
determined by one of the BWH epilepsy neurologists based on clinical seizure semiology
and/or EEG findings.

- Subjects who experience at least 1-2 seizures per month on average, are aware of or
have reliable caregivers who are aware of when seizures occur and can reliably log
seizure frequency

- Subjects who have the cognitive ability to read and understand the consent form,
describe any potential symptoms experienced during or after treatments.

Exclusion Criteria:

- Subjects with a cognitive or psychiatric disorder that limits the ability to give
informed consent or are unable to cooperate with testing

- Subjects with dementia or other progressive degenerative disease, delirium or active
psychosis

- Subjects with ferromagnetic materials in the head

- Subjects with severe cardiac disease, increased intracranial pressure, or a
Transcutaneous Electrical Nerve Stimulation (TENS) unit

- Subjects who have primary generalized epilepsy or non-epileptic seizures

- Subjects who have experienced status epilepticus in the 3 months leading up to
enrollment in the study

- Subjects (females) who are pregnant, or are of childbearing potential and not willing
to use reliable birth control during the treatment period.

- Subjects who are unable to get a brain MRI for any reason (implanted metal in body,
inability to lie still)

- Subjects with current brain tumors or an intracranial vascular lesion

- Subjects with severe, uncontrolled medical problems, such as diabetes mellitus,
hypertension, pulmonary or airway disease, heart failure, coronary artery disease, or
any other condition that poses a risk for the subject during participation.

- Subjects with holes in the treatment area of the skull from trauma or prior surgery

- Subjects with pacemakers, medication pumps, and other implanted electronic hardware.
If a subject has a working Vagal Nerve Stimulator in place, the device will be turned
off prior to each treatment session and then turned back on after each session.