Observational Study of the Structural-functional Connectome in Patients With Epilepsy

Over the past decade, the concept of the brain as a complex network has extremely influenced the way regarding how the latter is studied (Bartolomei et al., 2017). The structure of both structural and functional networks within the brain has been related to optimal brain functioning (Duma et al., 2022). This evolution of methods and approaches of investigation has directly impacted the study of epilepsy. An early conception of focal epilepsy was that it was related to the activity of the epileptogenic zone, which was identified as the generative element of seizures. However, what was previously considered focal was found to be network alterations at various levels, thus moving from the epileptogenic zone to the concept of the epileptogenic network. Alterations in both the structural and functional network, compared with a healthy control population, have been identified in various forms of epilepsy from focal to idiopathic generalized epilepsy (Lariviere et al., 2022, Zhang et al., 2009). Often the identification and removal of the epileptogenic network, turns out to be the elective therapy in drug-resistant focal epilepsies. The process of diagnosing and defining the epileptogenic network is still debated today. One of the most widely used methods is the implantation of intracranial electrodes for electroencephalographic recording of seizures (Bartolomei et al., 2017). This methodology carries with it several, albeit controlled, risks to the patient. New noninvasive approaches are being developed seeking to integrate information from structural neuroimaging and cortical electrical activity measured by high-density electroencephalography with external electrodes (Duma et al., 2021). These new approaches also include simulative approaches that exploit individualized information such as cortex geometry and patient-specific white matter connections (Courtiol et al. 2020). Thus, starting from a simple structural and diffusion MRI, which is done in routine clinical examinations, multiple localizing hypotheses of the epileptogenic network can be tested using simulative models and then compared with the real EEG signal as validation. Of great relevance is also to understand how the structural-functional connectome relates to cognitive function in patients with epilepsy, who have a high probability of presenting impaired functioning in one or more cognitive domains.

Study Overview

• Status: Recruiting
• Conditions: Epilepsy
• Intervention / Treatment: Diagnostic test: Functional and structural Connectome

• Study Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

• Study Contact: Name: Gian Marco Duma, PhD; Phone Number: +39 0438414248; Email: gianmarco.duma@lanostrafamiglia.it
• Study Contact Backup: Name: Darling Boachie; Phone Number: +39 0438 41242; Email: segreteriascientifica.medea.veneto@lanostrafamiglia.it

Study Locations

• Italy
  • Treviso
    • Conegliano, Treviso, Italy, 31015
      • Recruiting
      • IRCCS E.Medea
      • Contact: Duma Gian Marco, PhD; Phone Number: +39 0438414248; Email: gianmarco.duma@lanostrafamiglia.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Patients with focal epilepsy with drug resistance

Description

Inclusion Criteria:

• a diagnosis of focal or generalized epilepsy confirmed by specialist evaluation;
• at least one MRI scan of the brain that includes T1w
• at least one recording with resting state EEG
• age between 6 and 65 years at the time of the evaluation of the present study;
• ability to take part in a neuropsychological assessment.

Exclusion Criteria:

• vascular causes or non-low grade tumors as causes of epilepsy
• age different from the range 6-65 years
• neuroradiologic examination not complete
• absence of resting state recording
• inability to take part in a neuropsychological evaluation.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Epilepsy; Recording of resting state EEG and MRI	Diagnostic test: Functional and structural Connectome; Reconstruction of EEG derived functional relationship between brain regions (functional connectome). Reconstruction of thickness covariance across brain regions (structural connectome)
Control group; EEG resting state data recording	Diagnostic test: Functional and structural Connectome; Reconstruction of EEG derived functional relationship between brain regions (functional connectome). Reconstruction of thickness covariance across brain regions (structural connectome)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of regional alteration in the value of functional connectivity	By comparing the value of functional connectivity derived from the EEG, between Epilepsy and control group, it is possible to identify altered brain regions to non-invasively identify the epileptogenic area, improving the diagnostic process	once at recrutiment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measuring the spread of the epileptogenic network	In the Epilepsy group the correlation between the functional and the structural connectome identify the spreading of the epileptogenic network, and therefore the intensity of the pathology, guiding the diagnostic process	once at recrutiment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between the Rey Complex figure test and the regional functional alteration	The correlation between the Rey complex figure test measuring the memory efficiency and the regional functional connectivity provides a potential diagnostic tool helping the identification of the alteration of brain areas in relationship to the known impairment of memory in patients with epilepsy	once at recrutiment

Collaborators and Investigators

• Sponsor: IRCCS Eugenio Medea
• Investigators: Principal Investigator: Gian Marco Duma, PhD, IRCCS E. Medea

Study record dates

Study Major Dates

• Study Start (Actual): June 22, 2023
• Primary Completion (Estimated): November 22, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: March 20, 2024
• First Submitted That Met QC Criteria: March 20, 2024
• First Posted (Actual): March 27, 2024

Study Record Updates

• Last Update Posted (Actual): March 27, 2024
• Last Update Submitted That Met QC Criteria: March 20, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy
• Other Study ID Numbers: 12.2022

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
• product manufactured in and exported from the U.S.: No