Noninvasive Pre-surgical Evaluation of Patients With Focal Epilepsy and Establishment of a Normative Imaging Database

Objectives: The overall study objective is to compare the sensitivities and specificities of
morphometric analysis techniques using structural MRI images based on pre- and postsurgical
localization of epileptic foci in patients undergoing presurgical evaluation for medically
refractory epilepsy. To carry out these analyses, we aim to establish an age-stratified
normative imaging database using healthy volunteers. Additional objectives are to identify
abnormal networks in these patients using resting state fMRI/EEG and MEG/EEG, and to use
language and memory fMRI tasks to examine the effects of epileptogenic zones and surgery on
cognitive function and the networks associated with these functions.

Study population: 150 adults and children (age 8-65) with uncontrolled focal epilepsy, and
100 age-stratified healthy volunteers.

Design: A retrospective and prospective natural history study. Research procedures for
patients in this study include neuropsychological testing and 1-4 MRI sessions during
presurgical evaluation and an additional 1-3 MRI sessions and neuropsychological testing
approximately 12 months post-operatively. Research testing (such as research
neuropsychological tests or MRI scanning sequences) will be done during a visit for clinical
testing whenever possible, likely reducing the number of required visits. Patients will also
have optional MEG and 7T structural imaging. Data will also be obtained from patients who
have already undergone epilepsy surgery if they had procedures as outlined in the protocol
and are willing to share the data. Healthy volunteers will receive a subset of the
pre-operative procedures for patients, requiring at least 3 visits. In order to ensure
adequate data acquisition, subjects may be re-scanned up to three times for the portions of
the study in which they participated, possibly requiring additional visits.

Outcome measures:

The main outcomes will be establishment of normative values for morphometric analysis methods
in age-stratified normal controls, and comparison of the sensitivity and specificity of these
measures to pre- and postsurgical localization of the epileptogenic zone. Secondary outcome
measures will include determination of the sensitivity and specificity of source localization
using MEG/EEG and resting state fMRI/EEG, and to evaluate changes in activation during rest,
as well as language and memory fMRI tasks in patients pre- and postsurgically, to examine the
effects of epileptogenic zones and surgery on cognitive function and the networks underlying
these functions.

- INCLUSION CRITERIA FOR PATIENTS:

- Age 8-65 years old

- Evaluated or under evaluation for epilepsy surgery under protocol 18-N-0066,11-N-0051
or 16-N-0041

- Documentation of focal epilepsy based on MRI, EEG and/or ictal semiology

- Ability to give informed consent or have a legally authorized representative able to
give consent (for adults without consent capacity) or parent/guardian able to provide
informed consent (for a child).

INCLUSION CRITERIA FOR PATIENTS SOLELY CONTRIBUTING DATA:

- Had epilepsy surgery with presurgical evaluation under 18-N-0066

- Age 8-65 at the time of epilepsy surgery evaluation

- Had a preoperative structural brain MRI of the type used in this protocol

INCLUSION CRITERIA FOR HEALTHY VOLUNTEERS:

- Age 8-65 years old

- Ability to give informed consent or have a parent/guardian able to provide informed
consent if a child.

- Ability to cooperate with MRI scanning without anesthesia

EXCLUSION CRITERIA FOR PATIENTS:

- Contraindications to MRI or MEG studies (such as pacemakers, cochlear implants,
shrapnel, permanent eyeliner)

- Claustrophobia or anxiety disorders exacerbated by the MRI scanner

- Pregnancy. All females of childbearing potential must have a negative pregnancy test
prior to MRI scanning

EXCLUSION CRITERIA FOR PATIENTS SOLELY CONTRIBUTING DATA:

-Not able or willing to give consent or do not have an appropriate surrogate who can
provide consent

EXCLUSION CRITERIA FOR HEALTHY VOLUNTEERS:

- Contraindications to MRI or MEG studies (such as pacemakers, cochlear implants,
shrapnel, permanent eyeliner)

- Claustrophobia or anxiety disorders exacerbated by the MRI scanner

- Significant medical conditions that may affect the central nervous system, such as
psychiatric disorders (such as mood disorders, psychotic disorders, substance abuse or
dependence), significant neurologic disorders (such as brain injury, neurodegenerative
disorders, multiple sclerosis, stroke, movement disorders, epilepsy), or active
systemic disease that may affect the central nervous system (such as uncontrolled
hypertension, autoimmune disorders or other inflammatory disorders, neoplastic
disease)

- Use of centrally acting medications in the past 6 weeks, such as benzodiazepines,
barbiturates, antidepressants, beta-blockers, and drugs for treating epilepsy or
migraine

- Pregnancy. All females of childbearing potential must have a negative pregnancy test
prior to MRI scanning