Project

epilepsy; seizures; therapy; transcranial current stimulation; modulation

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

Active participation

Number	Title	Start	Funding scheme

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.