Clinical trial NCT03582345: Investigation of Human Epileptic Networks by fMRI
Official title: Investigation of Human Epileptic Networks by fMRI Based Effective Connectivity: a New Approach to Identify the Neuronal Drivers of the Pathological Activity in Surgically Remediable Epilepsies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Epilepsy
Lead sponsor: Azienda Unita' Sanitaria Locale Di Modena
Sponsor class: OTHER
Collaborators: name: Maggiore Bellaria Hospital, Bologna
First posted: 2018-07-11
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: cohort prospectic, open, non randomized
Primary purpose: DIAGNOSTIC

Brief summary: Background:

In the Emilia-Romagna Region approximately 19.000 people are affected by epilepsy. About 25% of epileptic patients are drug-resistant (DRE) and some of them are eligible for resective surgery of the epileptogenic zone (EZ). The precise EZ localization is crucial for a good surgical outcome. Intracranial EEG (icEEG) recordings remain the gold-standard to localise the EZ. New neuroimaging techniques, like simultaneous recording of functional MRI and EEG (EEG-fMRI), with advanced methodological approaches as effective connectivity analysis (i.e. Dynamic Causal Modelling-DCM) might improve the EZ localization.

Objectives:

(1) To develop a non-invasive protocol for the investigation of the epileptic network in patients with surgically remediable epilepsies; (2) To shed light on the patho-physiological mechanisms of drug resistance in DRE; (3) To provide a validation of effective connectivity applied to fMRI data in epilepsy.

Methods:

Two Research Units (RU1, RU2) will identify and characterize a cohort of DRE patients eligible for resective surgery. RU1 will be in charge to perform the EEG/fMRI coregistration and data analysis. RU2 will be responsible for the surgical resection of epileptic foci. IcEEG recordings will be performed at the Claudio Munari Epilepsy Center, Ospedale Niguarda, Milano. RU1\&RU2 will evaluate the fMRI data results and compare with icEEG findings or expert's surgical decision. The principle measures of outcome are: (a) percentage of concordance of fMRI results with icEEG findings or electro-clinical features in term epileptic network identification; (b) percentage of concordance between DCM findings and EZ/IZ localization; (c) percentage of concordance of DCM findings with icEEG or electro-clinical features regarding the causal hierarchy within the epileptic network.

Detailed description: Background:

About 25% of epileptic patients are drug-resistant (DRE) and some of them are eligible for resective surgery of the epileptogenic zone (EZ). The precise EZ localization is crucial for a good surgical outcome. Intracranial EEG (icEEG) recordings remain the gold-standard to localise the EZ. New neuroimaging techniques, like simultaneous recording of functional MRI and EEG (EEG-fMRI), with advanced methodological approaches as effective connectivity analysis (i.e. Dynamic Causal Modelling-DCM) might improve the EZ localization. This innovative tool will have the advantage to be non-invasive and safe with significant decrease of injuries, hospitalization, with a resulting favourable cost/benefit ratio.

Objectives:

(1) to provide a validation of effective connectivity applied to fMRI data in epilepsy. (2)To develop a non-invasive protocol for the investigation of the epileptic network in patients with surgically remediable epilepsies; (3) To shed light on the patho-physiological mechanisms of drug resistance in DRE.

Methods:

Two Research Units (RU1, RU2) will identify and characterize a cohort of DRE patients eligible for resective surgery. RU1 will perform patients' recruitment, presurgical evaluation and EEG/fMRI coregistration and data analysis. RU2 will perform patients' recruitment, presurgical evaluation and surgical resection of epileptic foci. IcEEG recordings will be performed at the Claudio Munari Epilepsy Center, Ospedale Niguarda, Milano . RU1\&RU2 will evaluate the fMRI data results and compare with icEEG findings or expert's surgical decision. The principle measures of outcome are: (a) percentage of concordance of fMRI results with icEEG findings or electro-clinical features in term epileptic network identification; (b) percentage of concordance between DCM findings and EZ/IZ localization; (c) percentage of concordance of DCM findings with icEEG or electro-clinical features regarding the causal hierarchy within the epileptic network.

Eligibility criteria: Inclusion Criteria:

- Adults patients (≥18yrs) diagnosed with DRE (drug-resistant epilepsy), candidate for epilepsy surgery who will undergo directly to the resection of the epileptic focus or to icEEG recordings for a better EZ definition

Exclusion Criteria:

* Patients with idiopathic generalized epilepsies;
* Patients with focal epilepsy responders to AED;
* Patients with refractory focal epilepsy but contraindicated to perform a MRI;
* Patients who refute to have the EEG-fMRI;
* Patients whose cognitive status is too impaired to complete the necessary study forms.

Primary outcomes:
measure: Epilectic network
timeFrame: months 3-18
measure: Causal hierarchy within the epileptogenic network
timeFrame: months 3-18
measure: Drug-resistance
timeFrame: months 3-18
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Azienda Unita' Sanitaria Modena
name: Anna Elisabetta Vaudano, MD
role: PRINCIPAL_INVESTIGATOR
References: