Clinical Utility of Automated Electric Source Imaging in Presurgical Evaluation (PROMAESIS)

Prospective Multicenter Study on Localization Accuracy and Clinical Utility of Automated Electric Source Imaging in Presurgical Evaluation( PROMAESIS)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Surgery; Refractory Epilepsy; Electroencephalography; Brain Imaging
• Intervention / Treatment: Diagnostic test: No electrical source imaging (ESI); Diagnostic test: Automated electrical source imaging (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.

• Study Type: Interventional
• Enrollment (Estimated): 250
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Austria
  • Linz, Austria
    • Kepler University Clinic
  • Salzburg, Austria
    • Christian Doppler Klinik
• Czechia
  • Czech Rebuplic
    • Prague, Czech Rebuplic, Czechia
      • Motol University Hospital
  • Czech Republic
    • Brno, Czech Republic, Czechia
      • Brno Epilepsy Center
• Denmark
  • Dianalund, Denmark, DK 4293
    • Danish Epilepsy Center
• Germany
  • Baden-Wurttemberg
    • Freiburg, Baden-Wurttemberg, Germany
      • Freiburg University
• Italy
  • Milano, Italy
    • Carlo Besta Institure
  • Venice, Italy
    • Valencia University Hospital
• Portugal
  • Coimbra, Portugal
    • Centro Hospitalar e Universitário de Coimbra
  • Lisbon, Portugal
    • Hospital de Santa Maria
• Romania
  • Bucharest, Romania
    • University Hospital Bucharest
• Spain
  • Barcelona, Spain, 08003
    • Hospital del Mar

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 99 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: No electrical source imaging (ESI); The multidisciplinary teams take decisions based on considering all data without ESI	Diagnostic test: No electrical source imaging (ESI); For all patients: MRI, semiology, visual interpretation of EEG, and in selected cases, PET, SPECT; Diagnostic test: Automated electrical source imaging (ESI); The automated source imaging consists of 2 phases; Automated detection of EDs; Source imaging of each spike cluster and seizure onset epoch.
Experimental: Automated Electrical source imaging (ESI); The multidisciplinary teams take decisions based on considering all data with ESI	Diagnostic test: No electrical source imaging (ESI); For all patients: MRI, semiology, visual interpretation of EEG, and in selected cases, PET, SPECT; Diagnostic test: Automated electrical source imaging (ESI); The automated source imaging consists of 2 phases; Automated detection of EDs; Source imaging of each spike cluster and seizure onset epoch.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Sensitivity and Specificity of automated ESI in presurgical evaluation.	For determining the the accuracy (sensitivity and specificity) of automated ESI, one year outcome after the operation will be calculated based on the defined criteria.; True Positive (TP): source is in the same sub-lobar region as the resection, seizure-free outcome; False Positive (FP): source is in the same sub-lobar region as the resection, not seizure-free outcome; True Negative (TN): source outside the sub-lobar region that was resected, not seizure-free outcome; False Negative (FN): source outside the sub-lobar region that was resected, seizure-free outcome.	2 Years
the clinical utility of ESI in management of the patient with medically refractory epilepsy	For determining the clinical utility, the percentage of patients in whom automated ESI change decision on patients management will be calculated.	2 years

Collaborators and Investigators

• Sponsor: Sándor Beniczky
• Collaborators: Hospital del Mar; Centro Hospitalar e Universitário de Coimbra, E.P.E.; Motol University Hospital, Prague; Filadelfia Epilepsy Hospital; Freiburg University; Brno Epilepsy Center; University Hospital Bucharest (Adult); Kepler University Clinic, Linz; Christian Doppler Klinik, Salzburg; Valencia University Hospital; Carlo Besta Institure, Milano; Hospital de Santa Maria, Lisbon
• Investigators: Principal Investigator: Ricardo Rocamora, MD, Hospital del Mar; Principal Investigator: Martin Pali, MD, Brno Epilepsy Center; Principal Investigator: Ioana Mindruta, MD, University Hospital Bucharest (Adult); Principal Investigator: Andreas Schulze Bonhage, MD, Freiburg University; Principal Investigator: Tim von Oertzen, MD, Kepler University Clinic, Linz; Principal Investigator: Vdym Gnatkovsky, MD, Carlo Besta Institure, Milano; Principal Investigator: Peter Marusic, MD, Motol University Hospital, Prague; Principal Investigator: Markus Leitinger, MD, Christian Doppler Klinik, Salzburg; Principal Investigator: Francisco Sales, MD, Centro Hospitalar e Universitário de Coimbra, E.P.E.; Principal Investigator: vicente villanueva, MD, Valencia University Hospital; Principal Investigator: Carla Bente, MD, Hospital de Santa Maria,

Publications and helpful links

General Publications

• Boon P, D'Have M, Vanrumste B, Van Hoey G, Vonck K, Van Walleghem P, Caemaert J, Achten E, De Reuck J. Ictal source localization in presurgical patients with refractory epilepsy. J Clin Neurophysiol. 2002 Oct;19(5):461-8. doi: 10.1097/00004691-200210000-00009.
• Brodbeck V, Spinelli L, Lascano AM, Wissmeier M, Vargas MI, Vulliemoz S, Pollo C, Schaller K, Michel CM, Seeck M. Electroencephalographic source imaging: a prospective study of 152 operated epileptic patients. Brain. 2011 Oct;134(Pt 10):2887-97. doi: 10.1093/brain/awr243.
• Beniczky S, Lantz G, Rosenzweig I, Akeson P, Pedersen B, Pinborg LH, Ziebell M, Jespersen B, Fuglsang-Frederiksen A. Source localization of rhythmic ictal EEG activity: a study of diagnostic accuracy following STARD criteria. Epilepsia. 2013 Oct;54(10):1743-52. doi: 10.1111/epi.12339. Epub 2013 Aug 14.
• Megevand P, Spinelli L, Genetti M, Brodbeck V, Momjian S, Schaller K, Michel CM, Vulliemoz S, Seeck M. Electric source imaging of interictal activity accurately localises the seizure onset zone. J Neurol Neurosurg Psychiatry. 2014 Jan;85(1):38-43. doi: 10.1136/jnnp-2013-305515. Epub 2013 Jul 30.
• Rikir E, Koessler L, Gavaret M, Bartolomei F, Colnat-Coulbois S, Vignal JP, Vespignani H, Ramantani G, Maillard LG. Electrical source imaging in cortical malformation-related epilepsy: a prospective EEG-SEEG concordance study. Epilepsia. 2014 Jun;55(6):918-32. doi: 10.1111/epi.12591. Epub 2014 Apr 4.
• Lascano AM, Perneger T, Vulliemoz S, Spinelli L, Garibotto V, Korff CM, Vargas MI, Michel CM, Seeck M. Yield of MRI, high-density electric source imaging (HD-ESI), SPECT and PET in epilepsy surgery candidates. Clin Neurophysiol. 2016 Jan;127(1):150-155. doi: 10.1016/j.clinph.2015.03.025. Epub 2015 May 9.
• Maliia MD, Meritam P, Scherg M, Fabricius M, Rubboli G, Mindruta I, Beniczky S. Epileptiform discharge propagation: Analyzing spikes from the onset to the peak. Clin Neurophysiol. 2016 Apr;127(4):2127-33. doi: 10.1016/j.clinph.2015.12.021. Epub 2016 Jan 12.
• Mouthaan BE, Rados M, Barsi P, Boon P, Carmichael DW, Carrette E, Craiu D, Cross JH, Diehl B, Dimova P, Fabo D, Francione S, Gaskin V, Gil-Nagel A, Grigoreva E, Guekht A, Hirsch E, Hecimovic H, Helmstaedter C, Jung J, Kalviainen R, Kelemen A, Kimiskidis V, Kobulashvili T, Krsek P, Kuchukhidze G, Larsson PG, Leitinger M, Lossius MI, Luzin R, Malmgren K, Mameniskiene R, Marusic P, Metin B, Ozkara C, Pecina H, Quesada CM, Rugg-Gunn F, Rydenhag B, Ryvlin P, Scholly J, Seeck M, Staack AM, Steinhoff BJ, Stepanov V, Tarta-Arsene O, Trinka E, Uzan M, Vogt VL, Vos SB, Vulliemoz S, Huiskamp G, Leijten FS, Van Eijsden P, Braun KP; E-PILEPSY consortium. Current use of imaging and electromagnetic source localization procedures in epilepsy surgery centers across Europe. Epilepsia. 2016 May;57(5):770-6. doi: 10.1111/epi.13347. Epub 2016 Mar 25.

Study record dates

Study Major Dates

• Study Start (Actual): March 12, 2019
• Primary Completion (Actual): May 1, 2021
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: December 30, 2019
• First Submitted That Met QC Criteria: January 2, 2020
• First Posted (Actual): January 6, 2020

Study Record Updates

• Last Update Posted (Actual): February 2, 2024
• Last Update Submitted That Met QC Criteria: February 1, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Accuracy; Epilepsy surgery; Sensitivity; Specificity; Refractory epilepsy; Clinical Utility; Automated ESI
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Drug Resistant Epilepsy
• Other Study ID Numbers: PROMAESIS

Drug and device information, study documents

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