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| ID | Type | Description | Link |
|---|---|---|---|
| UK/33/2022 | Other Grant/Funding Number | Comenius University |
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Epilepsy as a brain disease is characterised by enhanced brain excitability. Low frequency repetitive transcranial magnetic stimulation (rTMS) can be an effective treatment for refractory focal epilepsy. Today different ways of stimulation were used, the best protocol of rTMS in refractory focal epilepsy is under evaluation. The aim of our study is neuropsychological and electrophysiological evaluation before and after rTMS sessions, the results of rTMS will be compared with VNS outcome in patients, who undergoes VNS implantation after rTMS.
Background Epilepsy is a chronic disease that causes repetitive seizures. In 60% to 70% of people with epilepsy (PWE) , these seizures start in a small part of the brain (focal epilepsy). Up to 30% of people with epilepsy continue to have seizures despite optimal pharmacological care. Invasive methods - called epilepsy surgery are the choice of treatment for this group of the patients. New non- invasive non- pharmacological methods are on the way.
Aim of the study Treatment the people with focal epilepsy with non- invasive transcranial magnetic stimulation (rTMS) to the region that causes the epilepsy. A part of the patients will after that be treated with invasive VNS implantation. The aim is to evaluate neuropsychological and electrophysiological out come in non- invasive arm and in combined arm (VNS after rTMS).
Inclusion criteria The patients with neocortical focal epilepsy older than 18 years, not controlled with antiseizure drugs, with confirmed refractory epilepsy.
Study methodology The seizure frequency will be controlled with seizure diaries, patients will be evaluated in tertiary epilepsy centre. The patients will be on stable dose of drugs 4 week before and at least 8 weeks after last TMS session. They will be evaluated by battery of neuropsychological tests (cognition, emotions, personality) and electrophysiological methods ( QEEG, SEP n. medianus) before rTMS sessions and after rTMS session and a month later. A part of the patient, who will continue to VNS implantation will be evaluated before VNS implantation and 6 month later again.
The magnetic pulses will be delivered in a active session or in a placebo session ( sham). The investigators will not tell in which order they deliver the treatments.
What are the possible benefits and risks of participating? The investigators believe, that the patients will have fewer seizures in the weeks following the active treatment and that the improvement could be detected in neuropsychological evaluations and in electrophysiology. It is not known, if the results of rTMS could predict the response of the patients to VNS stimulation.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intervention/treatment | Experimental | figure-of-eight active rTMS coil rTMS is administered using the figure-of-eight active coil, at 90% of the resting motor threshold over the epileptogenic region, in trains with a total of 15000 pulses during 5 weekdays at low frequency 0,5Hz Device: figure-of-eight active rTMS coil navigated rTMS over epileptogenic focus using figure-of-eight active rTMS coil, optic navigation system |
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| Control arm | Sham Comparator | figure-of-eight active rTMS coil rTMS is administered using the figure-of-eight sham coil, at 90% of the resting motor threshold over the epileptogenic region, in trains with a total of 15000 pulses during 5 weekdays at sham stimulation Device: figure-of-eight sham rTMS coil navigated rTMS over epileptogenic focus using figure-of-eight sham rTMS coil, optic navigation system |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| figure-of-eight active rTMS coil device | Device | rTMS is administered using the figure-of-eight active coil, at 90% of the resting motor threshold over the epileptogenic region, in trains with a total of 15000 pulses during 5 weekdays at low frequency 0,5Hz Device: figure-of-eight active rTMS coil navigated rTMS over epileptogenic focus using figure-of-eight active rTMS coil, optic navigation system |
| Measure | Description | Time Frame |
|---|---|---|
| Seizure frequency and severity | 50% Responder Rate after active rTMS treatment and median of seizure frequency reduction from baseline according seizure diaries of the patients rated per 28 day period | 1 hour |
| Measure | Description | Time Frame |
|---|---|---|
| QOLIE-31-P measurement of different neuropsychological aspects of epilepsy | measurement of different neuropsychological aspects of epilepsy (cognition, emotions, social well- being and social functioning) in patients before and one month after rTMS: Questionnaires: Quality of Life in Epilepsy- problems (QOLIE-31-P) change of score | 20 min |
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Inclusion Criteria:
- fully characterized refractory focal neocortical epilepsy (i.e. the epileptogenic zone is well defined) on a stable drug regimen for at least one month, able to complete a seizure dairy either by the patient or by a significant other
Exclusion Criteria:
- Metal in the head including deep brain stimulators, aneurysmal clips, ventricular shunts, cochlear implants, ossicular reconstruction of the middle ear, VNS implants pacemaker, implantable cardioverter-defibrillator (ICD) psychogenic non-epileptic seizures and other non-epileptic spells
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 2nd Department of Neurology, Faculty of Medicine COMENIUS UNIVERSITY BRATISLAVA | Bratislava | Slovak Republic | 83305 | Slovakia |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22950513 | Background | Sun W, Mao W, Meng X, Wang D, Qiao L, Tao W, Li L, Jia X, Han C, Fu M, Tong X, Wu X, Wang Y. Low-frequency repetitive transcranial magnetic stimulation for the treatment of refractory partial epilepsy: a controlled clinical study. Epilepsia. 2012 Oct;53(10):1782-9. doi: 10.1111/j.1528-1167.2012.03626.x. Epub 2012 Sep 5. | |
| 17068786 |
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| ID | Term |
|---|---|
| D004828 | Epilepsies, Partial |
| D004827 | Epilepsy |
| D002493 | Central Nervous System Diseases |
| D001927 | Brain Diseases |
| ID | Term |
|---|---|
| D009422 | Nervous System Diseases |
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| figure-of-eight sham rTMS coil device | Device | rTMS is administered using the figure-of-eight sham coil, in trains with a total of 15000 pulses during 5 weekdays Device: figure-of-eight sham rTMS coil navigated rTMS over epileptogenic focus using figure-of-eight sham rTMS coil, optic navigation system |
|
| Electrophysiological evaluation with quantitative EEG |
Electrophysiological evaluation with quantitative EEG ( QEEG) as response to rTMS stimulation and correlation with primary outcome measure and neuropsychological outcome measured with neuropsychological batteries change in cordance |
| 30 min |
| Comparison the data in the group of the patients | Comparison the data in the group of the patients, who will after rTMS continue to VNS implantation, multiregression analysis for possible connection between rTMS response and later VNS efficacy | 1 hour |
| Drop out rate and adverse event profile | Drop out rate and adverse event profile | 1 hour |
| LSSS- measurement of different neuropsychological aspects of epilepsy | measurement of different neuropsychological aspects of epilepsy (cognition, emotions, social well- being and social functioning) in patients before and one month after rTMS: Liverpool seizure severity scale (LSSS) change in frequency and severity of seizures | 10 min |
| PHQ-9 measurement of different neuropsychological aspects of epilepsy | measurement of different neuropsychological aspects of epilepsy (cognition, emotions, social well- being and social functioning) in patients before and one month after rTMS: Patients Health Questionnaire ( PHQ-9), change of score | 5 min |
| GAD-7 measurement of different neuropsychological aspects of epilepsy | measurement of different neuropsychological aspects of epilepsy (cognition, emotions, social well- being and social functioning) in patients before and one month after rTMS: Generalized Anxiety Disorder(GAD-7), change of score | 5 min |
| ROCFT measurement of different neuropsychological aspects of epilepsy | measurement of different neuropsychological aspects of epilepsy (cognition, emotions, social well- being and social functioning) in patients before and one month after rTMS: Rey-Osterrieth complex figure test ( ROCFT), change of score | 10 min |
| STROOP measurement of different neuropsychological aspects of epilepsy | measurement of different neuropsychological aspects of epilepsy (cognition, emotions, social well- being and social functioning) in patients before and one month after rTMS: Stroop 1,2,3, change of score | 15 min |
| TMT AB measurement of different neuropsychological aspects of epilepsy | measurement of different neuropsychological aspects of epilepsy (cognition, emotions, social well- being and social functioning) in patients before and one month after rTMS: Trail making test A,B, (TMT AB), change of score | 5 min |
| DST measurement of different neuropsychological aspects of epilepsy | measurement of different neuropsychological aspects of epilepsy (cognition, emotions, social well- being and social functioning) in patients before and one month after rTMS: Digit span test (DST), change of score | 10 min |
| AVLT measurement of different neuropsychological aspects of epilepsy | measurement of different neuropsychological aspects of epilepsy (cognition, emotions, social well- being and social functioning) in patients before and one month after rTMS: Auditory verbal learning test ( AVLT), change of score | 10 min |
| MoCA measurement of different neuropsychological aspects of epilepsy | measurement of different neuropsychological aspects of epilepsy (cognition, emotions, social well- being and social functioning) in patients before and one month after rTMS: Montreal Cognitive Assessment (MoCA) change of score | 20 min |
| SDMT measurement of different neuropsychological aspects of epilepsy | measurement of different neuropsychological aspects of epilepsy (cognition, emotions, social well- being and social functioning) in patients before and one month after rTMS: Symbol Digit Modalities Test (SDMT), change of score | 10 min |
| StT measurement of different neuropsychological aspects of epilepsy | measurement of different neuropsychological aspects of epilepsy (cognition, emotions, social well- being and social functioning) in patients before and one month after rTMS: Story Test (StT), change of score | 10 min |
| WCST measurement of different neuropsychological aspects of epilepsy | measurement of different neuropsychological aspects of epilepsy (cognition, emotions, social well- being and social functioning) in patients before and one month after rTMS: Wisconsin Card Sorting Test (WCST), change of score | 10 min |
| Electrophysiological evaluation with quantitative SEP | Electrophysiological evaluation with SEP (n. medianus amplitude) as response to rTMS stimulation and correlation with primary outcome measure and neuropsychological outcome measured with neuropsychological batteries change of amplitude | 1 hour |
| Fregni F, Otachi PT, Do Valle A, Boggio PS, Thut G, Rigonatti SP, Pascual-Leone A, Valente KD. A randomized clinical trial of repetitive transcranial magnetic stimulation in patients with refractory epilepsy. Ann Neurol. 2006 Oct;60(4):447-55. doi: 10.1002/ana.20950. |
| 26970993 | Background | Pereira LS, Muller VT, da Mota Gomes M, Rotenberg A, Fregni F. Safety of repetitive transcranial magnetic stimulation in patients with epilepsy: A systematic review. Epilepsy Behav. 2016 Apr;57(Pt A):167-176. doi: 10.1016/j.yebeh.2016.01.015. Epub 2016 Mar 10. |
| 26642974 | Background | Seynaeve L, Devroye A, Dupont P, Van Paesschen W. Randomized crossover sham-controlled clinical trial of targeted low-frequency transcranial magnetic stimulation comparing a figure-8 and a round coil to treat refractory neocortical epilepsy. Epilepsia. 2016 Jan;57(1):141-50. doi: 10.1111/epi.13247. Epub 2015 Dec 8. |
| 17295632 | Background | Cantello R, Rossi S, Varrasi C, Ulivelli M, Civardi C, Bartalini S, Vatti G, Cincotta M, Borgheresi A, Zaccara G, Quartarone A, Crupi D, Lagana A, Inghilleri M, Giallonardo AT, Berardelli A, Pacifici L, Ferreri F, Tombini M, Gilio F, Quarato P, Conte A, Manganotti P, Bongiovanni LG, Monaco F, Ferrante D, Rossini PM. Slow repetitive TMS for drug-resistant epilepsy: clinical and EEG findings of a placebo-controlled trial. Epilepsia. 2007 Feb;48(2):366-74. doi: 10.1111/j.1528-1167.2006.00938.x. |
| 40782718 | Derived | Melus J, Waczulikova I, Hapakova L, Konecna M, Valkovic P, Timarova G. Repetitive transcranial magnetic stimulation for the treatment of focal drug-resistant epilepsy: A crossover, randomized, single-blinded, sham-controlled clinical trial. Seizure. 2025 Sep;131:290-297. doi: 10.1016/j.seizure.2025.07.015. Epub 2025 Jul 27. |