Harmonization of the pipeline for seizure detection to phenotype post-traumatic epilepsy in a preclinical multicenter study on post-traumatic epileptogenesis

Pablo M. Casillas-Espinosa, Pedro Andrade, Cesar Santana-Gomez, Tomi Paananen, Gregory Smith, Idrish Ali, Robert Ciszek, Xavier Ekolle Ndode-Ekane, Rhys D. Brady, Jussi Tohka, Matthew R. Hudson, Piero Perucca, Emma L. Braine, Riikka Immonen, Noora Puhakka, Sandy R. Shultz, Nigel C. Jones, Richard J. Staba, Asla Pitkänen, Terence J. O'Brien

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Rationale: The Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx) Centre without walls is an NIH funded multicenter consortium. One of EpiBioS4Rx projects is a preclinical post-traumatic epileptogenesis biomarker study that involves three study sites: The University of Eastern Finland, Monash University (Melbourne) and the University of California Los Angeles. Our objective is to create a platform for evaluating biomarkers and testing new antiepileptogenic treatments for post-traumatic epilepsy (PTE) using the lateral fluid percussion injury (FPI) model in rats. As only 30–50% of rats with severe lateral FPI develop PTE by 6 months post-injury, prolonged video-EEG monitoring is crucial to identify animals with PTE. Our objective is to harmonize the surgical and data collection procedures, equipment, and data analysis for chronic EEG recording in order to phenotype PTE in this rat model across the three study sites. Methods: Traumatic brain injury (TBI) was induced using lateral FPI in adult male Sprague-Dawley rats aged 11–12 weeks. Animals were divided into two cohorts: a) the long-term video-EEG follow-up cohort (Specific Aim 1), which was implanted with EEG electrodes within 24 h after the injury; and b) the magnetic resonance imaging (MRI) follow-up cohort (Specific Aim 2), at 5 months after lateral FPI. Four cortical epidural screw electrodes (2 ipsilateral, 2 contralateral) and three intracerebral bipolar electrodes were implanted (septal CA1 and the dentate gyrus, layers II and VI of the perilesional cortex both anterior and posterior to the injury site). During the 7th post-TBI month, animals underwent 4 weeks of continuous video-EEG recordings to diagnose of PTE. Results: All centers harmonized the induction of TBI and surgical procedures for the implantation of EEG recordings, utilizing 4 or more EEG recording channels to cover areas ipsilateral and contralateral to the brain injury, perilesional cortex and the hippocampus and dentate gyrus. Ground and reference screw electrodes were implanted. At all sites the minimum sampling rate was 512 Hz, utilizing a finite impulse response (FIR) and impedance below 10 KΩ through the entire recording. As part of the quality control criteria we avoided electrical noise, and monitoring changes in impedance over time and the appearance of noise on the recordings. To reduce electrical noise, we regularly checked the integrity of the cables, stability of the EEG recording cap and the appropriate connection of the electrodes with the cables. Following the pipeline presented in this article and after applying the quality control criteria to our EEG recordings all of the sites were successful to phenotype seizure in chronic EEG recordings of animals after TBI. Discussion: Despite differences in video-EEG acquisition equipment used, the three centers were able to consistently phenotype seizures in the lateral fluid-percussion model applying the pipeline presented here. The harmonization of methodology will help to improve the rigor of preclinical research, improving reproducibility of pre-clinical research in the search of biomarkers and therapies to prevent antiepileptogenesis.

Original languageEnglish
Number of pages10
JournalEpilepsy Research
DOIs
Publication statusAccepted/In press - 27 Apr 2019

Keywords

  • Common data elements
  • Electroencephalogram
  • Post-traumatic epilepsy
  • Seizures
  • Traumatic brain injury

Cite this

Casillas-Espinosa, Pablo M. ; Andrade, Pedro ; Santana-Gomez, Cesar ; Paananen, Tomi ; Smith, Gregory ; Ali, Idrish ; Ciszek, Robert ; Ndode-Ekane, Xavier Ekolle ; Brady, Rhys D. ; Tohka, Jussi ; Hudson, Matthew R. ; Perucca, Piero ; Braine, Emma L. ; Immonen, Riikka ; Puhakka, Noora ; Shultz, Sandy R. ; Jones, Nigel C. ; Staba, Richard J. ; Pitkänen, Asla ; O'Brien, Terence J. / Harmonization of the pipeline for seizure detection to phenotype post-traumatic epilepsy in a preclinical multicenter study on post-traumatic epileptogenesis. In: Epilepsy Research. 2019.
@article{9d7b9dc1b1e44132bdeacdef1ba1cc9d,
title = "Harmonization of the pipeline for seizure detection to phenotype post-traumatic epilepsy in a preclinical multicenter study on post-traumatic epileptogenesis",
abstract = "Rationale: The Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx) Centre without walls is an NIH funded multicenter consortium. One of EpiBioS4Rx projects is a preclinical post-traumatic epileptogenesis biomarker study that involves three study sites: The University of Eastern Finland, Monash University (Melbourne) and the University of California Los Angeles. Our objective is to create a platform for evaluating biomarkers and testing new antiepileptogenic treatments for post-traumatic epilepsy (PTE) using the lateral fluid percussion injury (FPI) model in rats. As only 30–50{\%} of rats with severe lateral FPI develop PTE by 6 months post-injury, prolonged video-EEG monitoring is crucial to identify animals with PTE. Our objective is to harmonize the surgical and data collection procedures, equipment, and data analysis for chronic EEG recording in order to phenotype PTE in this rat model across the three study sites. Methods: Traumatic brain injury (TBI) was induced using lateral FPI in adult male Sprague-Dawley rats aged 11–12 weeks. Animals were divided into two cohorts: a) the long-term video-EEG follow-up cohort (Specific Aim 1), which was implanted with EEG electrodes within 24 h after the injury; and b) the magnetic resonance imaging (MRI) follow-up cohort (Specific Aim 2), at 5 months after lateral FPI. Four cortical epidural screw electrodes (2 ipsilateral, 2 contralateral) and three intracerebral bipolar electrodes were implanted (septal CA1 and the dentate gyrus, layers II and VI of the perilesional cortex both anterior and posterior to the injury site). During the 7th post-TBI month, animals underwent 4 weeks of continuous video-EEG recordings to diagnose of PTE. Results: All centers harmonized the induction of TBI and surgical procedures for the implantation of EEG recordings, utilizing 4 or more EEG recording channels to cover areas ipsilateral and contralateral to the brain injury, perilesional cortex and the hippocampus and dentate gyrus. Ground and reference screw electrodes were implanted. At all sites the minimum sampling rate was 512 Hz, utilizing a finite impulse response (FIR) and impedance below 10 KΩ through the entire recording. As part of the quality control criteria we avoided electrical noise, and monitoring changes in impedance over time and the appearance of noise on the recordings. To reduce electrical noise, we regularly checked the integrity of the cables, stability of the EEG recording cap and the appropriate connection of the electrodes with the cables. Following the pipeline presented in this article and after applying the quality control criteria to our EEG recordings all of the sites were successful to phenotype seizure in chronic EEG recordings of animals after TBI. Discussion: Despite differences in video-EEG acquisition equipment used, the three centers were able to consistently phenotype seizures in the lateral fluid-percussion model applying the pipeline presented here. The harmonization of methodology will help to improve the rigor of preclinical research, improving reproducibility of pre-clinical research in the search of biomarkers and therapies to prevent antiepileptogenesis.",
keywords = "Common data elements, Electroencephalogram, Post-traumatic epilepsy, Seizures, Traumatic brain injury",
author = "Casillas-Espinosa, {Pablo M.} and Pedro Andrade and Cesar Santana-Gomez and Tomi Paananen and Gregory Smith and Idrish Ali and Robert Ciszek and Ndode-Ekane, {Xavier Ekolle} and Brady, {Rhys D.} and Jussi Tohka and Hudson, {Matthew R.} and Piero Perucca and Braine, {Emma L.} and Riikka Immonen and Noora Puhakka and Shultz, {Sandy R.} and Jones, {Nigel C.} and Staba, {Richard J.} and Asla Pitk{\"a}nen and O'Brien, {Terence J.}",
year = "2019",
month = "4",
day = "27",
doi = "10.1016/j.eplepsyres.2019.04.011",
language = "English",
journal = "Epilepsy Research",
issn = "0920-1211",
publisher = "Elsevier",

}

Harmonization of the pipeline for seizure detection to phenotype post-traumatic epilepsy in a preclinical multicenter study on post-traumatic epileptogenesis. / Casillas-Espinosa, Pablo M.; Andrade, Pedro; Santana-Gomez, Cesar; Paananen, Tomi; Smith, Gregory; Ali, Idrish; Ciszek, Robert; Ndode-Ekane, Xavier Ekolle; Brady, Rhys D.; Tohka, Jussi; Hudson, Matthew R.; Perucca, Piero; Braine, Emma L.; Immonen, Riikka; Puhakka, Noora; Shultz, Sandy R.; Jones, Nigel C.; Staba, Richard J.; Pitkänen, Asla; O'Brien, Terence J.

In: Epilepsy Research, 27.04.2019.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Harmonization of the pipeline for seizure detection to phenotype post-traumatic epilepsy in a preclinical multicenter study on post-traumatic epileptogenesis

AU - Casillas-Espinosa, Pablo M.

AU - Andrade, Pedro

AU - Santana-Gomez, Cesar

AU - Paananen, Tomi

AU - Smith, Gregory

AU - Ali, Idrish

AU - Ciszek, Robert

AU - Ndode-Ekane, Xavier Ekolle

AU - Brady, Rhys D.

AU - Tohka, Jussi

AU - Hudson, Matthew R.

AU - Perucca, Piero

AU - Braine, Emma L.

AU - Immonen, Riikka

AU - Puhakka, Noora

AU - Shultz, Sandy R.

AU - Jones, Nigel C.

AU - Staba, Richard J.

AU - Pitkänen, Asla

AU - O'Brien, Terence J.

PY - 2019/4/27

Y1 - 2019/4/27

N2 - Rationale: The Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx) Centre without walls is an NIH funded multicenter consortium. One of EpiBioS4Rx projects is a preclinical post-traumatic epileptogenesis biomarker study that involves three study sites: The University of Eastern Finland, Monash University (Melbourne) and the University of California Los Angeles. Our objective is to create a platform for evaluating biomarkers and testing new antiepileptogenic treatments for post-traumatic epilepsy (PTE) using the lateral fluid percussion injury (FPI) model in rats. As only 30–50% of rats with severe lateral FPI develop PTE by 6 months post-injury, prolonged video-EEG monitoring is crucial to identify animals with PTE. Our objective is to harmonize the surgical and data collection procedures, equipment, and data analysis for chronic EEG recording in order to phenotype PTE in this rat model across the three study sites. Methods: Traumatic brain injury (TBI) was induced using lateral FPI in adult male Sprague-Dawley rats aged 11–12 weeks. Animals were divided into two cohorts: a) the long-term video-EEG follow-up cohort (Specific Aim 1), which was implanted with EEG electrodes within 24 h after the injury; and b) the magnetic resonance imaging (MRI) follow-up cohort (Specific Aim 2), at 5 months after lateral FPI. Four cortical epidural screw electrodes (2 ipsilateral, 2 contralateral) and three intracerebral bipolar electrodes were implanted (septal CA1 and the dentate gyrus, layers II and VI of the perilesional cortex both anterior and posterior to the injury site). During the 7th post-TBI month, animals underwent 4 weeks of continuous video-EEG recordings to diagnose of PTE. Results: All centers harmonized the induction of TBI and surgical procedures for the implantation of EEG recordings, utilizing 4 or more EEG recording channels to cover areas ipsilateral and contralateral to the brain injury, perilesional cortex and the hippocampus and dentate gyrus. Ground and reference screw electrodes were implanted. At all sites the minimum sampling rate was 512 Hz, utilizing a finite impulse response (FIR) and impedance below 10 KΩ through the entire recording. As part of the quality control criteria we avoided electrical noise, and monitoring changes in impedance over time and the appearance of noise on the recordings. To reduce electrical noise, we regularly checked the integrity of the cables, stability of the EEG recording cap and the appropriate connection of the electrodes with the cables. Following the pipeline presented in this article and after applying the quality control criteria to our EEG recordings all of the sites were successful to phenotype seizure in chronic EEG recordings of animals after TBI. Discussion: Despite differences in video-EEG acquisition equipment used, the three centers were able to consistently phenotype seizures in the lateral fluid-percussion model applying the pipeline presented here. The harmonization of methodology will help to improve the rigor of preclinical research, improving reproducibility of pre-clinical research in the search of biomarkers and therapies to prevent antiepileptogenesis.

AB - Rationale: The Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx) Centre without walls is an NIH funded multicenter consortium. One of EpiBioS4Rx projects is a preclinical post-traumatic epileptogenesis biomarker study that involves three study sites: The University of Eastern Finland, Monash University (Melbourne) and the University of California Los Angeles. Our objective is to create a platform for evaluating biomarkers and testing new antiepileptogenic treatments for post-traumatic epilepsy (PTE) using the lateral fluid percussion injury (FPI) model in rats. As only 30–50% of rats with severe lateral FPI develop PTE by 6 months post-injury, prolonged video-EEG monitoring is crucial to identify animals with PTE. Our objective is to harmonize the surgical and data collection procedures, equipment, and data analysis for chronic EEG recording in order to phenotype PTE in this rat model across the three study sites. Methods: Traumatic brain injury (TBI) was induced using lateral FPI in adult male Sprague-Dawley rats aged 11–12 weeks. Animals were divided into two cohorts: a) the long-term video-EEG follow-up cohort (Specific Aim 1), which was implanted with EEG electrodes within 24 h after the injury; and b) the magnetic resonance imaging (MRI) follow-up cohort (Specific Aim 2), at 5 months after lateral FPI. Four cortical epidural screw electrodes (2 ipsilateral, 2 contralateral) and three intracerebral bipolar electrodes were implanted (septal CA1 and the dentate gyrus, layers II and VI of the perilesional cortex both anterior and posterior to the injury site). During the 7th post-TBI month, animals underwent 4 weeks of continuous video-EEG recordings to diagnose of PTE. Results: All centers harmonized the induction of TBI and surgical procedures for the implantation of EEG recordings, utilizing 4 or more EEG recording channels to cover areas ipsilateral and contralateral to the brain injury, perilesional cortex and the hippocampus and dentate gyrus. Ground and reference screw electrodes were implanted. At all sites the minimum sampling rate was 512 Hz, utilizing a finite impulse response (FIR) and impedance below 10 KΩ through the entire recording. As part of the quality control criteria we avoided electrical noise, and monitoring changes in impedance over time and the appearance of noise on the recordings. To reduce electrical noise, we regularly checked the integrity of the cables, stability of the EEG recording cap and the appropriate connection of the electrodes with the cables. Following the pipeline presented in this article and after applying the quality control criteria to our EEG recordings all of the sites were successful to phenotype seizure in chronic EEG recordings of animals after TBI. Discussion: Despite differences in video-EEG acquisition equipment used, the three centers were able to consistently phenotype seizures in the lateral fluid-percussion model applying the pipeline presented here. The harmonization of methodology will help to improve the rigor of preclinical research, improving reproducibility of pre-clinical research in the search of biomarkers and therapies to prevent antiepileptogenesis.

KW - Common data elements

KW - Electroencephalogram

KW - Post-traumatic epilepsy

KW - Seizures

KW - Traumatic brain injury

UR - http://www.scopus.com/inward/record.url?scp=85060275869&partnerID=8YFLogxK

U2 - 10.1016/j.eplepsyres.2019.04.011

DO - 10.1016/j.eplepsyres.2019.04.011

M3 - Article

JO - Epilepsy Research

JF - Epilepsy Research

SN - 0920-1211

ER -