Clinical trial NCT02560597: Repetitive Transcranial Magnetic Stimulation (rTMS) for the Treatment of Epilepsy
Official title: Repetitive Transcranial Magnetic Stimulation (rTMS) for the Treatment of Epilepsy - Case Study in Patients With Epilepsia Partialis Continua (EPC) and Refractory Status Epilepticus (SE)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Epilepsia Partialis Continua
Status Epilepticus
Keywords: epilepsy
epilepsia partialis continua
status epilepticus
treatment resistant
repetitive transcranial magnetic stimulation
Lead sponsor: University Hospital, Ghent
Sponsor class: OTHER
First posted: 2015-09-25
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 1. 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.
2. 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.
3. 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.
4. 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Seizure diary
timeFrame: Throughout the study, lasting approximately 4 weeks
measure: Electrographic epileptiform activity
timeFrame: Throughout the study, lasting approximately 4 weeks, with assessment before treatment (if possible) and after treatment
measure: Neurological examination
timeFrame: Throughout the study, lasting approximately 4 weeks
Secondary outcomes:
measure: Duration of the clinical effect
timeFrame: Throughout the study, lasting approximately 4 weeks or as long as the outlasting effect lasts
measure: Adverse events
timeFrame: Throughout the study, lasting approximately 4 weeks
Other outcomes:
Locations:
city: Ghent
country: Belgium
facility: University Hospital, Ghent
Study officials:
affiliation: University Hospital, Ghent
name: Alfred Meurs, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rotenberg A, Bae EH, Takeoka M, Tormos JM, Schachter SC, Pascual-Leone A. Repetitive transcranial magnetic stimulation in the treatment of epilepsia partialis continua. Epilepsy Behav. 2009 Jan;14(1):253-7. doi: 10.1016/j.yebeh.2008.09.007. Epub 2008 Oct 30.
citation: Morales OG, Henry ME, Nobler MS, Wassermann EM, Lisanby SH. Electroconvulsive therapy and repetitive transcranial magnetic stimulation in children and adolescents: a review and report of two cases of epilepsia partialis continua. Child Adolesc Psychiatr Clin N Am. 2005 Jan;14(1):193-210, viii-ix. doi: 10.1016/j.chc.2004.07.010.
citation: Misawa S, Kuwabara S, Shibuya K, Mamada K, Hattori T. Low-frequency transcranial magnetic stimulation for epilepsia partialis continua due to cortical dysplasia. J Neurol Sci. 2005 Jul 15;234(1-2):37-9. doi: 10.1016/j.jns.2005.03.035.
citation: Liu A, Pang T, Herman S, Pascual-Leone A, Rotenberg A. Transcranial magnetic stimulation for refractory focal status epilepticus in the intensive care unit. Seizure. 2013 Dec;22(10):893-6. doi: 10.1016/j.seizure.2013.06.014. Epub 2013 Jul 19.
citation: Thordstein M, Constantinescu R. Possibly lifesaving, noninvasive, EEG-guided neuromodulation in anesthesia-refractory partial status epilepticus. Epilepsy Behav. 2012 Nov;25(3):468-72. doi: 10.1016/j.yebeh.2012.07.026. Epub 2012 Sep 12.
citation: Graff-Guerrero A, Gonzales-Olvera J, Ruiz-Garcia M, Avila-Ordonez U, Vaugier V, Garcia-Reyna JC. rTMS reduces focal brain hyperperfusion in two patients with EPC. Acta Neurol Scand. 2004 Apr;109(4):290-6. doi: 10.1046/j.1600-0404.2003.00222.x.
citation: VanHaerents S, Herman ST, Pang T, Pascual-Leone A, Shafi MM. Repetitive transcranial magnetic stimulation; A cost-effective and beneficial treatment option for refractory focal seizures. Clin Neurophysiol. 2015 Sep;126(9):1840-2. doi: 10.1016/j.clinph.2014.12.004. Epub 2014 Dec 15. No abstract available.