Clinical trial NCT04218812: Clinical Utility of Automated Electric Source Imaging in Presurgical Evaluation
Official title: Prospective Multicenter Study on Localization Accuracy and Clinical Utility of Automated Electric Source Imaging in Presurgical Evaluation( PROMAESIS)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Electroencephalography
Refractory Epilepsy
Brain Imaging
Surgery
Keywords: Sensitivity
Specificity
Accuracy
Automated ESI
Refractory epilepsy
Epilepsy surgery
Clinical Utility
Lead sponsor: Aarhus University Hospital
Sponsor class: OTHER
Collaborators: name: Filadelfia Epilepsy Hospital
name: Hospital del Mar
name: Brno Epilepsy Center
name: University Hospital Bucharest (Adult)
name: Freiburg University
name: Kepler University Clinic, Linz
name: Motol University Hospital
name: Christian Doppler Klinik, Salzburg
name: Centro Hospitalar e Universitário de Coimbra, E.P.E.
name: Valencia University Hospital
name: Carlo Besta Institure, Milano
name: Hospital de Santa Maria, Lisbon
First posted: 2020-01-06
Enrollment: 250
Sex: ALL
Minimum age (years): 1
Maximum age (years): 99
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Evaluation of automated electrical source imaging(ESI) in epilepsy surgery.
Primary purpose: DIAGNOSTIC

Brief summary: Electrical source imaging is part of the presurgical evaluation of patients with drug-resistant focal epilepsy. The software packages that will be used in this study have Declaration of Conformity within the European Economic Area (CE mark) for this specific medical use. In spite of being part of the clinical standard, the evidence for the accuracy and clinical utility of these methods are derived from several smaller-scale and retrospective studies. The PROMAESIS study will provide solid evidence of the accuracy and clinical utility of automated ESI.

Detailed description: One-third of patients with epilepsy have seizures resistant to pharmacotherapy. There are many approaches developed to control these seizures, yet epilepsy surgery is still the most common method. The crucial part of epilepsy surgery is to assess the epileptic zone in order to render patients seizure free. However, accurate localization of the epileptic zone is often challenging due to the multimodal approach. This contains semiology, EEG (obtained during long term video-EEG monitoring), magnetic resonance Imaging (MRI), in addition to certain cases, positron emission computed tomography (PET), and single photon emission computed tomography (SPECT) and magnetoencephalography (MEG). At present, in one of the third patients, seizure remains after epilepsy surgery. Therefore a new preoperative method should be improved to assess the epileptic zone. Automated ESI is a post-processing novel method that estimates the location in the brain of the source of the recorded EEG signals.

The objective of this study is:

1. To determine the accuracy of ESI in localizing the epileptic focus.
2. To determine the clinical utility of ESI on clinical decision making

Methods:

Study design: a prospective diagnostic study in line with the Standards for Reporting Diagnostic Accuracy Studies (STARD).

EEG was recorded using the International Federation of Clinical Neurophysiology (IFCN) electrode array of 25 electrodes including six electrodes in the Inferior temporal chain (F9/10, T9/10, and P9/10) in addition to the 19 electrodes of the 10-20 system. Electrode impedance was kept below 5 kilo-ohm. EEG was recorded with a sampling frequency of 256 Hz. The investigators will make a video on how to place the electrodes, to make sure all centers follow a standardized method. Multidisciplinary epilepsy teams classify that in the first step you should keep the multidisciplinary team blinded to the source imaging data, and make the implantation plan without the ESI results. Then show the ESI, adjust the plan and note the changes.

The multidisciplinary teams in different centers will classify seizures into "types." A seizure type is a group of seizures that have stereotypical semiology and ictal EEG. Maximum 3 seizures are registered for per type. After Long Term Monitoring, they provide Epilog and Brain Electrical Source Analysis (BESA) teams with datasets including MRI and Long Term Monitoring recording for each patient. For uploading datasets, multicenter teams will use the platform developed by Epilog. Afterward, Epilog and BESA teams (blinded to patient information) will run the automated source imaging-both for interictal epileptiform discharge (EDs) and ictal signs. Both software packages have CE mark for ESI. Finally, the multidisciplinary teams take decisions in two steps:

I. Considering all data, except ESI II. Adding ESI to all other data.

At each step, the decisions are classified into one of the following categories:

1. Stop (operation not recommended)
2. Implantation of intracranial electrodes
3. Operation

In addition, the changes are classified into one of the following categories:

1. No change - but concordant with the decision.
2. No change - but discordant with decision.
3. Change from stop to implantation.
4. Change from implantation to stop.
5. Change in implantation plan: implantation of additional sites (besides the ones planned in step-1).
6. Change from implantation of operation.
7. Change from operation to implantation.
8. Other (specify in free text). If changes are not related to all analyses results, it will be noted, which method(s) triggered the change (SLORETA-interictal / ictal; Equivalent Current Dipole - interictal/ictal; CLARA interictal/ictal).

At one-year follow-up, the changes are categorized as useful or not useful. A change is defined useful as follows: (a) change from stop to Intracranial Recording: the Intracranial Recording localized the source; (b) change in implantation strategy: the electrode(s) implanted based on the source imaging identified the source; (c) change from implantation to operation: the patient became seizure-free.

Eligibility criteria: Inclusion Criteria:

* Patients with drug resistant focal epilepsy, admitted to Epilepsy Monitoring Unit for presurgical evaluation, who are afterwards discussed at the multidisciplinary epilepsy surgery team meetings.

Exclusion Criteria:

* Patients who did not have a seizure during the monitoring.

Primary outcomes:
measure: The Sensitivity and Specificity of automated ESI in presurgical evaluation.
timeFrame: 2 Years
measure: the clinical utility of ESI in management of the patient with medically refractory epilepsy
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Linz
country: Austria
facility: Kepler University Clinic
city: Salzburg
country: Austria
facility: Christian Doppler Klinik
city: Prague
country: Czechia
facility: Motol University Hospital
state: Czech Rebuplic
city: Brno
country: Czechia
facility: Brno Epilepsy Center
state: Czech Republic
city: Dianalund
country: Denmark
facility: Danish Epilepsy Center
city: Freiburg
country: Germany
facility: Freiburg University
state: Baden-Wurttemberg
city: Milano
country: Italy
facility: Carlo Besta Institure
city: Venice
country: Italy
facility: Valencia University Hospital
city: Coimbra
country: Portugal
facility: Centro Hospitalar e Universitário de Coimbra
city: Lisbon
country: Portugal
facility: Hospital de Santa Maria
city: Bucharest
country: Romania
facility: University Hospital Bucharest
city: Barcelona
country: Spain
facility: Hospital del Mar
Study officials:
affiliation: Hospital del Mar
name: Ricardo Rocamora, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Brno Epilepsy Center
name: Martin Pali, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital Bucharest (Adult)
name: Ioana Mindruta, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Freiburg University
name: Andreas Schulze Bonhage, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Kepler University Clinic, Linz
name: Tim von Oertzen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Carlo Besta Institure, Milano
name: Vdym Gnatkovsky, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Motol University Hospital
name: Peter Marusic, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Christian Doppler Klinik, Salzburg
name: Markus Leitinger, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centro Hospitalar e Universitário de Coimbra, E.P.E.
name: Francisco Sales, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Valencia University Hospital
name: vicente villanueva, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital de Santa Maria,
name: Carla Bente, MD
role: PRINCIPAL_INVESTIGATOR
References:
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