Cortical Excitability in Post-traumatic Epilepsy

Measures of Cortical Excitability in Patients With Post-traumatic Epilepsy, Traumatic Brain Injury Patients Without Epilepsy, and Healthy Controls: a Pilot Study

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

Study Overview

• Status: Recruiting
• Conditions: Epilepsy; Traumatic Brain Injury; Cortical Excitability

Detailed Description

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)

• Study Type: Observational
• Enrollment (Anticipated): 30

Contacts and Locations

• Study Contact: Name: Ivana Tyrlikova; Phone Number: 3015309744; Email: tyrlikovai@epilepsydc.com
• Study Contact Backup: Name: Pavel Klein, MD; Phone Number: 3015309744; Email: kleinp@epilepsydc.com

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Recruiting
      • Mid-Atlantic Epilepsy and Sleep Center
      • Contact: Pavel Klein, MD; Phone Number: 3015309744; Email: kleinp@epilepsydc.com
      • Contact: Ivana Tyrlikova; Phone Number: 301-530-9744; Email: tyrlikovai@epilepsydc.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

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

Description

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.)

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Subjects with TBI and PTE; 10 subjects with a history of TBI, diagnosed with PTE (post-traumatic epilepsy). PTE is defined as acquired epilepsy with seizures that developed within ten years of TBI with no other clear cause
Subjects with TBI, no PTE; 10 subjects with a history of TBI, and 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
Healthy volunteers; 10 healthy volunteers; absent epilepsy or TBI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To compare the cortical excitability in subjects with TBI, TBI with PTE, subjects without TBI and epilepsy	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.	2-10 years after TBI

Collaborators and Investigators

• Sponsor: Mid-Atlantic Epilepsy and Sleep Center, LLC
• Collaborators: Alexander Rotenberg, M.D., Ph.D

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2022
• Primary Completion (Anticipated): August 31, 2023
• Study Completion (Anticipated): August 31, 2024

Study Registration Dates

• First Submitted: August 24, 2022
• First Submitted That Met QC Criteria: August 25, 2022
• First Posted (Actual): August 26, 2022

Study Record Updates

• Last Update Posted (Actual): August 26, 2022
• Last Update Submitted That Met QC Criteria: August 25, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Epilepsy; Brain Injuries; Brain Injuries, Traumatic; Epilepsy, Post-Traumatic
• Other Study ID Numbers: maesc011

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No