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Transcranial electrical current stimulation as a treatment in epilepsy

English title Transcranial electrical current stimulation as a treatment in epilepsy
Applicant Seeck Margitta
Number 163398
Funding scheme Project funding
Research institution Département de Neurosciences Cliniques Hôpitaux Universitaires de Genève Université de Genève
Institution of higher education University of Geneva - GE
Main discipline Neurology, Psychiatry
Start/End 01.06.2016 - 31.01.2022
Approved amount 474'000.00
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Keywords (5)

epilepsy; seizures; therapy; transcranial current stimulation; modulation

Lay Summary (German)

Lead
Epilepsy is one of the most common neurological conditions and in Switzerland around 40,000 patients are concerned. 40-50% of patients with epilepsy continue to experience seizures despite adequate drug treatment. Even if a certain percentage may benefit from surgery, there still remains an important number of around 15'000 patients in Switzerland which are left with refractory epilepsy. Here we aim to develop a non-invasive epilepsy treatment for those who do not respond to drugs and are not surgical candidates.
Lay summary

Neuromodulation (NM) ist eine Therapieoption, die in den letzten 20 Jahren ein großes Interesse im Bereich der Epilepsietherapie gewonnen hat. Derzeit sind nur zwei NM Methoden zugelassen, die beide invasiv sind: Vagusnerv- und Tiefenhirn-Stimulation des vorderen Thalamus-Hirnkerns. Es gibt jedoch ganz neue technische Entwicklungen, die im Rahmen der Epilepsietherapie interessant sind. Transkranielle Gleichstromstimulation (tDCS) hemmt neuronale Erregung an der Kathode and könnte daher auch epileptische Aktivität vermindern. Transkranielle Stimulation durch Wechselstrom (tACS) ist ähnlich, jedoch alternierend in einer festen Frequenz und soll auch eher hemmend wirken. Beide Techniken sind sicher und gut verträglich und wurden mit Erfolg in der kognitiven und Rehabilitations- Forschung angewendet. Auf dem Gebiet der Epilepsie gibt es jedoch nur sehr wenige Studien.

Mit unserem Projekt evaluieren wir prospektiv, ob tDCS und tACS die Anfallsaktivität mindern. Wir lokalisieren zuerst den epileptischen Fokus des Patienten mittels „High Density Elektroenzephalogramms“ mit 256 Elektroden, im Gehirn des Patienten, rekonstruiert auf der Basis des MRT des Patienten. Dann berechnen wir die Scalp-Elektroden Konfiguration, die stimuliert werden muss, um den Fokus im Gehirn des Patienten optimal zu erreichen. TDCS und tACS werden dann über diese Elektroden appliziert, in Einzel- oder mehrtägigen Sitzungen. Wir berechnen dann, ob und wie viele Anfälle oder EEG –Anomalien durch aktive Stimulation reduziert wurden, verglichen mit ineffizienter Scheinstimulation, wobei dieselben Elektroden sowohl zur Stimulation als auch für die EEG-Aufnahme benutzt werden.  Falls sich epileptische Anfälle mit dieser maßgeschneiderten nicht-invasiven NM signifikant reduzieren lassen könnten, würde den Erwachsenen- und Kinder-Neurologen eine weitere wirksame Therapie zur Verfügung stehen.

 

Direct link to Lay Summary Last update: 07.01.2016

Responsible applicant and co-applicants

Employees

Publications

Publication
Clinical phenotype modulates brain’s myelin and iron content in temporal lobe epilepsy
Roggenhofer Elisabeth, Toumpouli Evdokia, Seeck Margitta, Wiest Roland, Lutti Antoine, Kherif Ferath, Novy Jan, Rossetti Andrea O., Draganski Bogdan (2022), Clinical phenotype modulates brain’s myelin and iron content in temporal lobe epilepsy, in Brain Structure and Function, 227(3), 901-911.
Insular Stimulation Produces Mental Clarity and Bliss
Nencha Umberto, Spinelli Laurent, Vulliemoz Serge, Seeck Margitta, Picard Fabienne (2022), Insular Stimulation Produces Mental Clarity and Bliss, in Annals of Neurology, 91(2), 289-292.
The ENIGMA‐Epilepsy working group: Mapping disease from large data sets
Sisodiya Sanjay M., Whelan Christopher D., Hatton Sean N., Huynh Khoa, Altmann Andre, Ryten Mina, Vezzani Annamaria, Caligiuri Maria Eugenia, Labate Angelo, Gambardella Antonio, Ives‐Deliperi Victoria, Meletti Stefano, Munsell Brent C., Bonilha Leonardo, Tondelli Manuela, Rebsamen Michael, Rummel Christian, Vaudano Anna Elisabetta, Wiest Roland, Balachandra Akshara R., Bargalló Núria, Bartolini Emanuele, Bernasconi Andrea, Bernasconi Neda, et al. (2022), The ENIGMA‐Epilepsy working group: Mapping disease from large data sets, in Human Brain Mapping, 43(1), 113-128.
Increased delta power as a scalp marker of epileptic activity: a simultaneous scalp and intracranial electroencephalography study
De Stefano Pia, Carboni Margherita, Marquis Renaud, Spinelli Laurent, Seeck Margitta, Vulliemoz Serge (2022), Increased delta power as a scalp marker of epileptic activity: a simultaneous scalp and intracranial electroencephalography study, in European Journal of Neurology, 29(1), 26-35.
Evidence accumulation relates to perceptual consciousness and monitoring
Pereira Michael, Megevand Pierre, Tan Mi Xue, Chang Wenwen, Wang Shuo, Rezai Ali, Seeck Margitta, Corniola Marco, Momjian Shahan, Bernasconi Fosco, Blanke Olaf, Faivre Nathan (2021), Evidence accumulation relates to perceptual consciousness and monitoring, in Nature Communications, 12(1), 3261-3261.
Automated interictal source localisation based on high-density EEG
Vorderwülbecke Bernd J., Baroumand Amir G., Spinelli Laurent, Seeck Margitta, van Mierlo Pieter, Vulliémoz Serge (2021), Automated interictal source localisation based on high-density EEG, in Seizure, 92, 244-251.
Slow oscillations open susceptible time windows for epileptic discharges
Sheybani Laurent, Mégevand Pierre, Spinelli Laurent, Bénar Christian G., Momjian Shahan, Seeck Margitta, Quairiaux Charles, Kleinschmidt Andreas, Vulliémoz Serge (2021), Slow oscillations open susceptible time windows for epileptic discharges, in Epilepsia, 62(10), 2357-2371.
Safety and Efficacy of Coma Induction Following First-Line Treatment in Status EpilepticusA 2-Center Study
De Stefano Pia, Baumann Sira Maria, Semmlack Saskia, Rüegg Stephan, Marsch Stephan, Seeck Margitta, Sutter Raoul (2021), Safety and Efficacy of Coma Induction Following First-Line Treatment in Status EpilepticusA 2-Center Study, in Neurology, 97(6), e564-e576.
High-Density EEG in Current Clinical Practice and Opportunities for the Future
Stoyell Sally M., Wilmskoetter Janina, Dobrota Mary-Ann, Chinappen Dhinakaran M., Bonilha Leonardo, Mintz Mark, Brinkmann Benjamin H., Herman Susan T., Peters Jurriaan M., Vulliemoz Serge, Seeck Margitta, Hämäläinen Matti S., Chu Catherine J. (2021), High-Density EEG in Current Clinical Practice and Opportunities for the Future, in Journal of Clinical Neurophysiology, 38(2), 112-123.
Ictal EEG source localization in focal epilepsy: Review and future perspectives
van Mierlo Pieter, Vorderwülbecke Bernd J., Staljanssens Willeke, Seeck Margitta, Vulliémoz Serge (2020), Ictal EEG source localization in focal epilepsy: Review and future perspectives, in Clinical Neurophysiology, 131(11), 2600-2616.
Brain networks involved in generalized periodic discharges (GPD) in post-anoxic-ischemic encephalopathy
De Stefano Pia, Carboni Margherita, Pugin Deborah, Seeck Margitta, Vulliémoz Serge (2020), Brain networks involved in generalized periodic discharges (GPD) in post-anoxic-ischemic encephalopathy, in Resuscitation, 155, 143-151.
Seizure outcome and use of antiepileptic drugs after epilepsy surgery according to histopathological diagnosis: a retrospective multicentre cohort study
Lamberink Herm J, Otte Willem M, Blümcke Ingmar, Braun Kees P J, Aichholzer Martin, Amorim Isabel, Aparicio Javier, Aronica Eleonora, Arzimanoglou Alexis, Barba Carmen, Beck Jürgen, Becker Albert, Beckervordersandforth Jan C, Bien Christian G, Blümcke Ingmar, Bodi Istvan, Braun Kees PJ, Catenoix Helene, Chassoux Francine, Chipaux Mathilde, Cloppenborg Thomas, Coras Roland, Cross J Helen, De Palma Luca, et al. (2020), Seizure outcome and use of antiepileptic drugs after epilepsy surgery according to histopathological diagnosis: a retrospective multicentre cohort study, in The Lancet Neurology, 19(9), 748-757.
Detection of epileptic activity in presumably normal EEG
Baldini Sara, Pittau Francesca, Birot Gwenael, Rochas Vincent, Tomescu Miralena I, Vulliémoz Serge, Seeck Margitta (2020), Detection of epileptic activity in presumably normal EEG, in Brain Communications, 2(2), 1-10.
Electric source imaging for presurgical epilepsy evaluation: current status and future prospects
Mégevand Pierre, Seeck Margitta (2020), Electric source imaging for presurgical epilepsy evaluation: current status and future prospects, in Expert Review of Medical Devices, 17(5), 405-412.
Focal EEG changes indicating critical illness associated cerebral microbleeds in a Covid-19 patient
De Stefano Pia, Nencha Umberto, De Stefano Ludovico, Mégevand Pierre, Seeck Margitta (2020), Focal EEG changes indicating critical illness associated cerebral microbleeds in a Covid-19 patient, in Clinical Neurophysiology Practice, 5, 125-129.
Accuracy of Interictal and Ictal Electric and Magnetic Source Imaging: A Systematic Review and Meta-Analysis
Sharma Praveen, Seeck Margitta, Beniczky Sándor (2019), Accuracy of Interictal and Ictal Electric and Magnetic Source Imaging: A Systematic Review and Meta-Analysis, in Frontiers in Neurology, 10, 1-10.
The predictive value of hypometabolism in focal epilepsy: a prospective study in surgical candidates
Tomás José, Pittau Francesca, Hammers Alexander, Bouvard Sandrine, Picard Fabienne, Vargas Maria Isabel, Sales Francisco, Seeck Margitta, Garibotto Valentina (2019), The predictive value of hypometabolism in focal epilepsy: a prospective study in surgical candidates, in European Journal of Nuclear Medicine and Molecular Imaging, 46(9), 1806-1816.
Human amygdala response to unisensory and multisensory emotion input: No evidence for superadditivity from intracranial recordings
Domínguez-Borràs Judith, Guex Raphaël, Méndez-Bértolo Constantino, Legendre Guillaume, Spinelli Laurent, Moratti Stephan, Frühholz Sascha, Mégevand Pierre, Arnal Luc, Strange Bryan, Seeck Margitta, Vuilleumier Patrik (2019), Human amygdala response to unisensory and multisensory emotion input: No evidence for superadditivity from intracranial recordings, in Neuropsychologia, 131, 9-24.
Postoperative memory prognosis in temporal lobe epilepsy surgery: The contribution of postictal memory
Sveikata Lukas, Kavan Nicole, Pegna Alan J., Seeck Margitta, Assal Frederic, Momjian Shahan, Schaller Karl, Vulliemoz Serge (2019), Postoperative memory prognosis in temporal lobe epilepsy surgery: The contribution of postictal memory, in Epilepsia, 60(8), 1639-1649.
Interictal epileptogenic zone localization in patients with focal epilepsy using electric source imaging and directed functional connectivity from low‐density EEG
Coito Ana, Biethahn Silke, Tepperberg Janina, Carboni Margherita, Roelcke Ulrich, Seeck Margitta, Mierlo Pieter, Gschwind Markus, Vulliemoz Serge (2019), Interictal epileptogenic zone localization in patients with focal epilepsy using electric source imaging and directed functional connectivity from low‐density EEG, in Epilepsia Open, 4(2), 281-292.
European trends in epilepsy surgery
Baud Maxime O., Perneger Thomas, Rácz Attila, Pensel Max C., Elger Christian, Rydenhag Bertil, Malmgren Kristina, Cross J. Helen, McKenna Grainne, Tisdall Martin, Lamberink Herm J., Rheims Sylvain, Ryvlin Philippe, Isnard Jean, Mauguière François, Arzimanoglou Alexis, Akkol Serdar, Deniz Kaancan, Ozkara Cigdem, Lossius Morten, Rektor Ivan, Kälviäinen Reetta, Vanhatalo Lotta-Maria, Dimova Petia, et al. (2018), European trends in epilepsy surgery, in Neurology, 91(2), e96-e106.
Neural Sources and Underlying Mechanisms of Neural Responses to Heartbeats, and their Role in Bodily Self-consciousness: An Intracranial EEG Study
Park Hyeong-Dong, Bernasconi Fosco, Salomon Roy, Tallon-Baudry Catherine, Spinelli Laurent, Seeck Margitta, Schaller Karl, Blanke Olaf (2018), Neural Sources and Underlying Mechanisms of Neural Responses to Heartbeats, and their Role in Bodily Self-consciousness: An Intracranial EEG Study, in Cerebral Cortex, 28(7), 2351-2364.
Automated long-term EEG analysis to localize the epileptogenic zone
van Mierlo Pieter, Strobbe Gregor, Keereman Vincent, Birot Gwénael, Gadeyne Stefanie, Gschwind Markus, Carrette Evelien, Meurs Alfred, Van Roost Dirk, Vonck Kristl, Seeck Margitta, Vulliémoz Serge, Boon Paul (2017), Automated long-term EEG analysis to localize the epileptogenic zone, in Epilepsia Open, 2(3), 322-333.
Current standards of neuropsychological assessment in epilepsy surgery centers across Europe
Vogt Viola Lara, Äikiä Marja, del Barrio Antonio, Boon Paul, Borbély Csaba, Bran Ema, Braun Kees, Carette Evelien, Clark Maria, Cross Judith Helen, Dimova Petia, Fabo Daniel, Foroglou Nikolaos, Francione Stefano, Gersamia Anna, Gil-Nagel Antonio, Guekht Alla, Harrison Sue, Hecimovic Hrvoje, Heminghyt Einar, Hirsch Edouard, Javurkova Alena, Kälviäinen Reetta, Kavan Nicole, et al. (2017), Current standards of neuropsychological assessment in epilepsy surgery centers across Europe, in Epilepsia, 58(3), 343-355.

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
BAsler Epilepsietag Talk given at a conference Fahreignung bei Epilepsie aus globaler Sicht 19.08.2021 Basel, Switzerland Seeck Margitta;
European Academy of Neurology Talk given at a conference Epilepsy surgery: timing and preventing adverse outcome 25.05.2020 virtual meeting , Austria Seeck Margitta;
Baltic Congress of Neurology Talk given at a conference the future of epilepsy surgery 06.09.2018 Kauans, Lithuania Seeck Margitta;


Associated projects

Number Title Start Funding scheme
113766 Transcranial Magnetic Stimulation (TMS): A new tool in epilepsy treatment 01.01.2007 Project funding

Abstract

1.SummaryActive epilepsy is one of the most frequent neurological conditions in all ages, affecting around 40’000 patients in Switzerland. 40-50% patients with epilepsy continue to have seizures despite adequate antiepileptic medication. While a subset of patients can be operated, with good to excellent outcome, there is still a significant proportion of patients who require additional treatments. Neuromodulation is an alternative option, which has raised interest in the last 10-20 years. In Switzerland, currently only invasive neuromodulation including vagal nerve stimulation (VNS) and deep brain stimulation (DBS) of the anterior thalamic nuclei are accepted therapies , but while both decrease significantly seizures per month in 40% of the treated patients, < 5% are permanently seizure-free. Due to the invasive nature, and overall an unclear benefit for the individual patient, only few patients and caretakers demand VNS or DBS. Among non-invasive tools, low frequency repetitive transcranial magnetic stimulation (rTMS) received probably most of the attention, but failed to show significant clinical efficacy, and is moderately tolerated. Its modest effect is supposedly due to the lack of non-tailored stimulation regimen and/or only superficial interference with pathological neuronal activity. Recently, there have been advances in the technical development to overcome these limitations. Cathodal transcranial direct current stimulation (tDCS) decreases firing rates and hyperpolarizes neurons, whereas anodal tDCS exerts the contrary effects. Both anodal and cathodal tDCS techniques have been employed successfully in cognitive research and neurorehabilition (Krause & Cohen Kadosh, 2013), but there are only few small studies and case-reports on epilepsy which report, in the majority, positive results. Safety and tolerability have been documented in all studies, with the only major side effect of minor tingling/itching sensation at the stimulation site. Transcranial alternating current stimulation (tACS) uses the same set-up, stimulating at a fixed frequency, and both electrodes serve as either anode or cathode. Similar to tDCS, tACS in healthy controls is known for excellent safety and tolerability.In this project we aim at evaluating transcranial electrical current stimulation as a treatment for patients with epilepsy in a prospective study, taking into account the individual epileptic focus site. Targets can be localized with high density electrical source imaging (HD-ESI) using 256 electrodes, a technique which is well established in our center and is known to have an excellent precision, including deeper structures. Based on a head model taking into account the different tissue properties, which will be computed on the basis of the patient’s own MRI, we will determine the best set of stimulating electrodes to reach the epileptic source and stimulate the focus a tailored fashion by using the same 256-EEG set-up. Preliminary results of tDCS, using simple standard arrays, have shown excellent safety and tolerability also in epilepsy patients, in adults and children, and good efficacy up to 4 weeks compared to sham condition. Regarding tACS, there are no studies yet in patients with epilepsy, but in analogy to the invasive studies, high frequency stimulation should be beneficial.Particularly we aim to carry out 4 different work-packages:1.study single application of high-density tDCS and tACS in a cohort of selected patients with unifocal epilepsy and compare the effect with sham stimulation.2.study single application of high-density tDCS and tACS in a cohort of selected patients with multifocal epilepsy and compare the effect with sham stimulation. This is a particularly interesting study group because these patients are rarely surgical candidates, but suffer often from drug-resistant daily seizures. 3.In patients who showed good to excellent response in WP1 and WP2, daily sessions of stimulation for 5 days will be offered. 4.study the effect of tDCS on the alteration of the so-called attentional map on neuropsychological performance and the induced modification of global brain connectivity as determined in resting state EEG in healthy controls.Included population will be epileptic patients, children and adults, evaluated in our center and healthy volunteers who are able to undergo our stimulation protocol, with a duration of total of 2-2.5 h per session. In the patient population, the presence of epileptogenic activity will be quantified by charting the seizures, interictal discharges and so-called epileptogenic microstates (i.e. maps resembling the spikes, but without visible epileptogenic activity). Up to now, only very few patients benefitted from tailored neuromodulation. With the present study we like to fill the gap, and expect to markedly increase the yield of neuromodulation. Drug-refractory epilepsy is still a significant clinical unresolved problem. If seizures can be successfully controlled with non-invasive neuromodulatory therapy, this would be major achievement and add another powerful tool in the armamentarium of the neurologist/epileptologist or neuropediatrician.
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