Project

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Chronobiology of Seizure Risk in Epilepsy

Applicant Baud Maxime
Number 179929
Funding scheme Ambizione
Research institution Klinik und Poliklinik für Neurologie Inselspital
Institution of higher education University of Berne - BE
Main discipline Neurophysiology and Brain Research
Start/End 01.11.2018 - 31.10.2022
Approved amount 963'009.00
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All Disciplines (2)

Discipline
Neurophysiology and Brain Research
Pathophysiology

Keywords (7)

Chronobiology; Cortical excitability; Steroid hormones; ElectroEncephaloGraphy; Epilepsy; Optogenetics; Sleep-wake cycle

Lay Summary (French)

Lead
L’épilepsie est une maladie fréquente définie par la récurrence spontanée de crises qui semblent survenir de façon aléatoire et représentent une menace constante pour les patients. Récemment, l’utilisation de données longitudinales d’EEG sur des années, nous a permis de montrer de façon statistique que leur survenue n’est en fait pas aléatoire, mais plutôt cyclique. Ce projet explore les mécanismes physiologiques qui pourraient être à la base des cycles dans l’épilepsie.
Lay summary

Contenu et objectifs du travail de recherche

Dans une approche translationnelle nous étudions les cycles de crises chez les patients atteints d’épilepsie et dans des modèles d’épilepsie chez la souris. Les enregistrements électro-encéphalographiques (EEG) directement dans le tissu cérébral permet une documentation précise de la survenue des crises et de l’activité épileptique entre les crises. Nous corrélons cette activité cérébrale pathologique avec des cycles hormonaux, le cycle circadien et le cycle veille-sommeil. Les observations faites servent au développement d’algorithmes qui permettront d’anticiper les périodes pendant lesquelles le risque de crise est élevé.

Contexte scientifique et social du projet de recherche

Aujourd’hui avec l’avènement de l’âge digital et la miniaturisation de l’électronique, l’EEG chronique implanté va jouer un rôle central dans le monitorage de l’épilepsie et la personnalisation de la prise en charge. Avec un accès à une information continue sur leur propre maladie, les patients deviendront les acteurs centraux de la prise en charge.

Direct link to Lay Summary Last update: 22.08.2018

Responsible applicant and co-applicants

Employees

Publications

Publication
Chance and risk in epilepsy
Baud Maxime O., Proix Timothée, Rao Vikram R., Schindler Kaspar (2020), Chance and risk in epilepsy, in Current Opinion in Neurology, 1-1.
Endogenous multidien rhythm of epilepsy in rats
Baud Maxime O., Ghestem Antoine, Benoliel Jean-Jacques, Becker Christel, Bernard Christophe (2019), Endogenous multidien rhythm of epilepsy in rats, in Experimental Neurology, 315, 82-87.

Collaboration

Group / person Country
Types of collaboration
University of California San Francisco United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Geneva Wyss Center for neurotechnologies Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Industry/business/other use-inspired collaboration

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Dreilander Tagung Epilepise Talk given at a conference Neurostimulation in epilepsy 08.05.2020 BASEL, Switzerland Baud Maxime;
International Conference for Technology and Analysis of Seizures (ICTALS) Talk given at a conference Cycles in epilepsy 09.09.2019 Exceter, Great Britain and Northern Ireland Baud Maxime;
Engineering in Medicine and Biology Conference (EMBC) Talk given at a conference Cycles modulating seizure risk 23.07.2019 Berlin, Germany Baud Maxime;
International Conference on Epilepsy (ICE) Talk given at a conference Cycles modulating seizure risk 22.06.2019 Bangkok, Thailand Baud Maxime;
Deutsche Gesellschaft fur klinische Neurophysiologie Talk given at a conference Chronic EEG outside the hospital 29.03.2019 Freiburg, Germany Baud Maxime;


Knowledge transfer events

Active participation

Title Type of contribution Date Place Persons involved
The Spirit of Bern Workshop 27.02.2020 Bern, Switzerland Baud Maxime;
Woche des Gehirn Talk 12.03.2019 Bern, Switzerland Baud Maxime;


Abstract

Epilepsy is a common neurological disorder defined by the seemingly random occurrence of seizures. Without the ability to anticipate seizure timing, patients are plagued by constant uncertainty. Clinical observations suggest that Seizure Risk (Sz-risk, the variable probability of a seizure) is not uniform over time but rather influenced by fluctuating, patient-specific factors, including stress, circadian time, sleep-wake cycles, and hormonal changes. Such factors likely determine dynamic Sz-risk by modulating Cortical Excitability (CE) - the variable cortical response to a probing stimulus. Recently, using chronic intracranial EEG for years (cEEG), I studied the timing of thousands of seizures in ambulatory patients, an unprecedented opportunity. I unraveled that Sz-risk and Interictal Epileptiform Activity (IEA, the rate of epilepsy-related transient EEG waveforms) are modulated by well-known circadian rhythms, but also by multidien rhythms (over multiple days). Thus, IEA is a biomarker for Sz-risk over long time-scales, and reflects fluctuating CE. As a logical next step, I propose to characterize systemic influences on Cortical excitability, IEA and Seizure risk. In a translational effort, I will explore two parallel aims in epilepsy patients and a mouse model of seizures. Identifying systemic modulators of CE has groundbreaking potential for novel pharmacological strategies with broad applications to chronic cyclical brain disorders (epilepsy, migraine, mood disorders, etc.). In epilepsy, reliable seizure forecasting remains a major goal that is achievable with modern technology and may enable adjunct therapy targeted to periods of heightened Sz-risk.
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