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

Status Epilepticus Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02560597
• Other study ID #: EC2015/0083
• Status: Terminated
• Phase: N/A
• Start date: February 3, 2015
• Est. completion date: September 2018

Study information

• Verified date: January 2022
• Source: University Hospital, Ghent
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: September 2018
• Est. primary completion date: March 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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)

Related Conditions & MeSH terms

• Epilepsia Partialis Continua
• Epilepsy
• Status Epilepticus

Intervention

Procedure:
• repetitive transcranial magnetic stimulation
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.

Locations

Country	Name	City	State
Belgium	University Hospital, Ghent	Ghent

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Ghent

Country where clinical trial is conducted

Belgium, 

References & Publications (7)

Graff-Guerrero A, Gonzáles-Olvera J, Ruiz-García M, Avila-Ordoñez U, Vaugier V, García-Reyna JC. rTMS reduces focal brain hyperperfusion in two patients with EPC. Acta Neurol Scand. 2004 Apr;109(4):290-6. — View 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. — View 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. — View 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. Review. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Seizure diary	Self-reported seizure frequency throughout the study as a measure of clinical efficacy.	Throughout the study, lasting approximately 4 weeks
Primary	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
Primary	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	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
Secondary	Adverse events	Assessment of the adverse events associated with rTMS in EPC/SE.	Throughout the study, lasting approximately 4 weeks