Transcranial Magnetic Stimulation (TMS) in Genetic Epilepsies

Use of Transcranial Magnetic Stimulation (TMS) as a Surrogate of Pathophysiology in Genetic Epilepsies

Transcranial magnetic stimulation (TMS) uses electromagnetic induction as an efficient, painless, non-invasive method to generate a suprathreshold current at the level of the encephalon, and provide in vivo measurements of cortical excitability and reactivity at the level of the motor cortex (TMS-EMG) or the entire cortical mantle (TMS-EEG). This study proposes TMS measurements as a diagnostic tool in patients to understand mechanisms of epileptogenesis related to genetic mutations, and prognostic to guide and monitor precision treatments.

Study Overview

• Status: Recruiting
• Conditions: Epilepsy; Genetic Disease
• Intervention / Treatment: Diagnostic test: transcranial magnetic stimulation (TMS)

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Simona Balestrini, MD; Phone Number: 0555662719; Email: simona.balestrini@meyer.it
• Study Contact Backup: Name: Renzo Guerrini, MD; Phone Number: 0555662573; Email: renzo.guerrini@meyer.it

Study Locations

• Italy
  • Firenze, Italy
    • Recruiting
    • Meyer Children's Hospital IRCCS
    • Contact: Simona Balestrini, MD; Email: simona.balestrini@meyer.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Children aged >3 years and adults
• Diagnosis of epilepsy with presumed or confirmed genetic etiology. Diagnosis of genetic epilepsy is made by next-generation sequencing (NGS) analysis
• or Diagnosis of primary (non-hemicranial) headache, in the absence of alterations on neuroimaging, and no known genetic condition
• Obtaining informed consent

Exclusion Criteria:

• Age <3 years
• Presence of contraindications to TMS: history of head or eye trauma with inclusion of metal fragments, cardiac pacemaker, arrhythmic heart disease, hearing implants, implantation of drug delivery devices, piercings or tattoos with metallic ink.
• Pregnancy status

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Genetic epilepsy; Patients with epilepsies of genetic etiology	Diagnostic test: transcranial magnetic stimulation (TMS); The STM9000 Standard-BI stimulator with 70 mm refrigerated butterfly stimulator (EB Neuro, Florence, Italy) controlled by Galileo Netbrain 9000 hardware and software (EB Neuro, Florence, Italy) is used. EMG data are recorded from the contralateral dorsal first interosseous muscle using gelled surface electrodes. EEG data are recorded by using the BE PLUS PRO Advanced EEG/EMG/EP amplifier (EB Neuro, Florence, Italy IT).
Experimental: Patients with primary headache; Patients with primary headache with non-migraine features	Diagnostic test: transcranial magnetic stimulation (TMS); The STM9000 Standard-BI stimulator with 70 mm refrigerated butterfly stimulator (EB Neuro, Florence, Italy) controlled by Galileo Netbrain 9000 hardware and software (EB Neuro, Florence, Italy) is used. EMG data are recorded from the contralateral dorsal first interosseous muscle using gelled surface electrodes. EEG data are recorded by using the BE PLUS PRO Advanced EEG/EMG/EP amplifier (EB Neuro, Florence, Italy IT).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Resting motor threshold	Resting motor threshold (%MSO)	24 months
SICI	Short Interval intracortical inhibition (ratio)	24 months
ICF	Intracortical facilitation (ratio)	24 months
LICI	Long Interval Intracortical inhibition (ratio)	24 months
TEP amplitude	Amplitude of each component of the TMS-evoked potential (mV)	24 months
TEP latency	Latency of each component of the TMS-evoked potential (msec)	24 months

Collaborators and Investigators

• Sponsor: Meyer Children's Hospital IRCCS

Study record dates

Study Major Dates

• Study Start (Actual): November 22, 2023
• Primary Completion (Estimated): November 30, 2025
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: February 15, 2024
• First Submitted That Met QC Criteria: February 27, 2024
• First Posted (Actual): February 28, 2024

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 27, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Genetic Diseases, Inborn
• Other Study ID Numbers: TMSpath; RF-2021-12372804 (Other Grant/Funding Number: Italian Ministry of Health)

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