| Eligibility |
Inclusion Criteria:
Patients who are able and willing to give consent and able to attend all study visits.
Seizure refractory to at least three standard antiepileptic medications at adequate doses,
failed for lack of efficacy. This may include a rescue medication designated use as PRN.
A minimum of 3 seizures per month for 2 months by patient diary started at intake
interview.
Subjects should have focal seizures with or without secondary generalization. Subjects
should have evidence suggesting the focus within the periventricular white matter, basal
ganglia, thalamus, hypothalamus, or mesial temporal lobe has been previously determined as
the source of seizures by standard clinical criteria including at least the description of
seizures, physical examination, neuroimaging, and video EEG monitoring capturing at least
one seizure.
Subjects must be taking 2 medications during the Baseline period and the dosage must be
stable.
A diagnosis of intractable lesional epilepsy which may include: Hypothalamic hamartoma,
Periventricular nodular hetereotopia, Dysembryoplastic neuroepithelial tumor (DNET),
Cortical dysplasia, Tuberous sclerosis, Focal cortical gliosis, or Predominately unilateral
Mesial Temporal Lobe Epilepsy (MTLE).
Exclusion Criteria:
Patients with unstable cardiac status that would increase anesthetic risk including:
unstable angina pectoris on medication, documented myocardial infarction within six months
of protocol entry, congestive heart failure requiring medication (other than diuretic),
anti-arrhythmic drug use.
Patients exhibiting any behavior(s) consistent with ethanol or substance abuse as defined
by the criteria outlined in the DSM-IV as manifested by one (or more) of the following
occurring within a 12 month period:
Recurrent substance use resulting in a failure to fulfill major role obligations at work,
school, or home (such as repeated absences or poor work performance related to substance
use; substance-related absences, suspensions, or expulsions from school; or neglect of
children or household, Recurrent substance use in situations in which it is physically
hazardous (such as driving an automobile or operating a machine when impaired by substance
use), Recurrent substance-related legal problems (such as arrests for substance related
disorderly conduct), Continued substance use despite having persistent or recurrent social
or interpersonal problems caused or exacerbated by the effects of the substance (for
example, arguments with spouse about consequences of intoxication and physical fights).
Severe hypertension (diastolic BP > 100 on medication) measured at intake interview or on
Treatment Day.
Patients with standard contraindications for MR imaging such as non-MRI compatible
implanted metallic devices including cardiac pacemakers, size limitations, etc.
Known intolerance or allergies to the MRI contrast agent (i.e. Gadavist) including advanced
kidney disease.
Known or suspected sensitivity to perfluetren (Definity®). Severely impaired renal function
(estimated glomerular filtration rate < 45ml/min/1.73 m2) or receiving dialysis.
History of abnormal bleeding and/or coagulopathy. Receiving anticoagulant (e.g. warfarin)
or antiplatelet (e.g. aspirin) therapy within one week of focused ultrasound procedure or
drugs known to increase risk of hemorrage (e.g. Avastin) within one month of focused
ultrasound procedure; or, unable or unwilling to stop anticoagulant for the purposed of
focused ultrasound procedure.
Active or suspected acute or chronic uncontrolled infection. History of intracranial
hemorrhage. Cerebrovascular disease (multiple CVA or CVA within 6 months). Individuals who
are not able or willing to tolerate the required prolonged stationary supine position
during treatment (can be up to 4 hrs of total table time).
Symptoms and signs of increased intracranial pressure (e.g. headache, nausea, vomiting,
lethargy, and papilledema).
Are participating or have participated in another clinical trial in the last 30 days.
Presence of any other neurodegenerative disease. Present of cognitive impairment severe
enough to be unable to understand and consent for the study, or understand the procedures.
History of immunocompromise, including patient who is HIV positive. Known life-threatening
systemic disease. Patient with current or a prior history of current suicidal ideation or
previous suicide attempt within the past year.
Patients with risk factors for intraoperative or postoperative bleeding (platelet count
less than 100,000 per cubic millimeter, PT > 14, PTT > 36 or INR > 1.3) or a documented
coagulopathy.
Patients with malignant brain tumors. Any illness that in the investigator's opinion
precludes participation in this study.
Pregnancy or lactation. Legal incapacity or limited legal capacity. Patients with a known
history of psychogenic non-epileptic spells in the last three years.
Patients with a vagal nerve stimulator (that is not MRI-safe and/or MRI compatible), deep
brain stimulator, other implanted electronic device, or prior radiofrequency lesion
techniques.
Patient with cardiopulmonary or vascular illness that would complicate anesthesia.
Patients who are unwilling to undergo general anesthesia. Patients with lesions in the
brainstem or cerebellum. Patients with symptomatic generalized epilepsy. Patients with only
simple partial seizures. Patients who have had convulsive status epilepticus within 12
months prior to baseline.
Patients with a prior diagnosis of psychogenic/non-epileptic seizures within the last 5
years.
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