To test whether measures of cortical excitability derived from motor cortex transcranial magnetic stimulation (TMS) in patients with traumatic brain injury reflect heightened excitability relative to healthy controls and whether such measures can be used to distinguish patients with post-traumatic epilepsy from patients with head trauma but no epilepsy

This is a pilot a pilot cross-sectional study to evaluate the utility of TMS-derived biomarkers in PTE prediction and detection. We will measure motor cortex excitability and intracortical inhibition (see below) in TBI patients with PTE (Group 1), TBI patients with average 30% risk of developing PTE who have not yet developed PTE (Group 2) and healthy age- and sex-matched control participants (group 3). 10 adult subjects aged 18-70 will be recruited into each group. We shall obtain a range of TMS metrics in each individual (see below), and, per metric, compare average values among groups by 1-way ANOVA. Our specific hypothesis is that, relative to healthy control, motor cortex TMS measures will indicate increased cortical excitability in participants with PTE, and a trend toward same in patients with TBI who have not developed PTE For subjects in groups 2 and 3, all antiseizure treatments will be stable (unchanged) for 4 weeks prior to evaluation. Subjects will undergo two ppTMS testing separated by 1-2 weeks. Per participant, TMS metrics (see below), will be evaluated for test-retest reliability (our secondary outcome measure)

Inclusion Criteria:

Group 1 (N=10):

• Age 18-70
• Sex: male/female
• PTE, defined as acquired epilepsy with seizures that developed within ten years of TBI with no other clear cause
• Stable ASM doses for at least 30 days
• Epilepsy duration for ≥ 6 months

Group 2 (N=10):

• Age 18-70

• Sex: male/female

• Absent epilepsy, but TBI in the past two years and any of the following:

  • Multifocal intracerebral hemorrhages (ICH)
  • depressed skull fracture
  • Subdural hematoma (SDH) requiring surgery
  • SDH and ICH
  • Penetrating wound

Group 3 (N=10):

• Age 18-70
• Sex: male/female
• Absent epilepsy or TBI

Exclusion Criteria:

1. Primary generalized epilepsy
2. Non-epileptic seizures
3. Progressive neurological disease including neoplasm, CNS degenerative disorders including Alzheimer's disease, other forms of dementia
4. Any systemic illness or unstable medical condition that might pose additional risk, including renal or liver disease, clinically uncontrolled cardiac disease, other unstable metabolic or endocrine disturbances, and active systemic cancer
5. Change in dose of any antiseizure medication within 30 days prior to enrollment
6. Active drug or alcohol dependence or any other factors that, in the opinion of the site investigators that would interfere with adherence to study requirements;
7. Use of any CNS-active investigational drugs within 1 month of enrollment.
8. Resective epilepsy surgery less than 6 months before study initiation.
9. Implanted electrical device (e.g. vagal nerve stimulator, deep brain stimulator, responsive neurostimulation device, cardiac pacemeaker, etc.)

Subjects will be recruited from the site's database, plus 10 healthy volunteers