Repetitive Transcranial Magnetic Stimulation (rTMS) for the Treatment of Epilepsy

Study Overview
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Brief Summary
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The purpose of this study is to assess the effects of repetitive transcranial magnetic stimulation (rTMS) as a treatment for Epilepsia Partialis Continua (EPC) or refractory Status Epilepticus (SE), when standard clinical treatments have failed.

Detailed Description
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Study design: This is a case study, including up to 10 patients with EPC or refractory SE that are admitted to the service in the coming 5 years. If circumstances permit so, a baseline evaluation of seizure frequency over 1 week and a 24-hour baseline EEG registration will be obtained, as well as a baseline clinical neurologic exam. In case of therapeutic urgency, these baseline measurements will be omitted. The treatment itself consists of multiple stimulation sessions over multiple days, decided upon based on patient characteristics and the obtained effects. In absence of the desired effect, treatment will be repeated during 5 consecutive days at most. Patients will be followed-up clinically and electrographically. In case of therapeutic success, the treatment can be repeated over time when seizures reoccur. Objectives: The primary objective of this study is to evaluate the effect of rTMS on the clinical status of patients with continuous refractory focal seizures (either EPC or SE). A beneficial effect on clinical status is defined as a decrease in seizure frequency or an interruption of continuous electrographic epileptiform activity, as well as an improvement in consciousness or other cortical functions that are disturbed by the EPC or SE (motor function, speech,...). As a secondary objective, the duration of the induced therapeutic effect will be evaluated, as well as the effect of rTMS on epileptiform discharges and the associated side effects and tolerability of the treatment. Stimulation: The exact stimulation protocol will be decided upon case per case, based on similar reports in literature. The optimal stimulation protocol is currently unknown. Rationale: Patients with EPC often have a high number of debilitating seizures per day that are hard to control with anti-epileptic medication. Some cases of SE also do not respond to standard care and require heavy sedation of the patient. Some of these patient may benefit from treatment with rTMS, which is painless, non-invasive and safe and can be administered at bedside. Moreover, in patients with EPC en SE, the (almost) continuous ictal activity allows an immediate effect evaluation.

Official Title
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Repetitive Transcranial Magnetic Stimulation (rTMS) for the Treatment of Epilepsy - Case Study in Patients With Epilepsia Partialis Continua (EPC) and Refractory Status Epilepticus (SE)

Conditions
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Epilepsia Partialis Continua, Status Epilepticus

Intervention / Treatment
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* Procedure: repetitive transcranial magnetic stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Epilepsia partialis continua or refractory status epilepticus Prior investigations (EEG, MRI...) show a well-defined neocortical epileptogenic focus Informed consent signed by the patient or his/her legal representative Exclusion Criteria: Pregnancy, short-term birth wish or childbearing age without adequate birth control Intracranial metal hardware (excluding dental filling): surgical clips, shrapnell, electrodes under the stimulation area Presence of pacemaker, implantable cardioverter-defibrillator (ICD), permanent medication pumps, cochlear implants or deep brain stimulation (DBS)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: repetitive transcranial magnetic stimulation<br>rTMS delivered over the epileptogenic focus | Procedure: repetitive transcranial magnetic stimulation<br>* Stimulation over the epileptogenic focus using variable stimulation protocols as described in literature. This protocol may vary case by case, depending on patient characteristics and achieved effect from previous stimulation. In absence of effect, rTMS is given on 5 consecutive days at most.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seizure diary | Self-reported seizure frequency throughout the study as a measure of clinical efficacy. | Throughout the study, lasting approximately 4 weeks | 
| Electrographic epileptiform activity | Interictal or continuous epileptiform activity on EEG is assessed throughout the study as a measure of clinical efficacy. | Throughout the study, lasting approximately 4 weeks, with assessment before treatment (if possible) and after treatment | 
| Neurological examination | Neurological examination assessing consciousness and other cortical functions that are potentially disturbed by the EPC or SE (eg. motor function, speech,...) is performed throughout the study as a measure of clinical efficacy. | Throughout the study, lasting approximately 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of the clinical effect | In case a beneficial clinical effect is obtained, an assessment of the duration of this effect will be performed. | Throughout the study, lasting approximately 4 weeks or as long as the outlasting effect lasts | 
| Adverse events | Assessment of the adverse events associated with rTMS in EPC/SE. | Throughout the study, lasting approximately 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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epilepsy, epilepsia partialis continua, status epilepticus, treatment resistant, repetitive transcranial magnetic stimulation