Transcranial Magnetic Stimulation for Rolandic Epilepsy

(TMS4BECTS Trial)

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Stanford University

Disqualifiers: Prematurity, Serious neurologic problems, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 2 weeks

36 Participants Needed

Trial Summary

What is the purpose of this trial?

Benign epilepsy with centrotemporal spikes (BECTS) is the most common pediatric epilepsy syndrome. Affected children typically have a mild seizure disorder, but yet have moderate difficulties with language, learning and attention that impact quality of life more than the seizures. Separate from the seizures, these children have very frequent abnormal activity in their brain known as interictal epileptiform discharges (IEDs, or spikes), which physicians currently do not treat. These IEDs arise near the motor cortex, a region in the brain that controls movement. In this study, the investigators will use a form of non-invasive brain stimulation called transcranial magnetic stimulation (TMS) to determine the impact of IEDs on brain regions important for language to investigate: (1) if treatment of IEDs could improve language; and (2) if brain stimulation may be a treatment option for children with epilepsy. Participating children will wear electroencephalogram (EEG) caps to measure brain activity. The investigators will use TMS to stimulate the brain region where the IEDs originate to measure how this region is connected to other brain regions. Children will then receive a special form of TMS called repetitive TMS (rTMS) that briefly reduces brain excitability. The study will measure if IEDs decrease and if brain connectivity changes after rTMS is applied. The investigators hypothesize that the IEDs cause language problems by increasing connectivity between the motor cortex and language regions. The investigators further hypothesize that rTMS will reduce the frequency of IEDs and also reduce connectivity between the motor and language region

Do I need to stop my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications. It is best to consult with the trial coordinators for more information.

What data supports the idea that Transcranial Magnetic Stimulation for Rolandic Epilepsy is an effective treatment?

The available research shows that Transcranial Magnetic Stimulation (TMS) has been studied for its effects on epilepsy, but not specifically for Rolandic Epilepsy. Some studies have shown that TMS can reduce certain brain activities linked to seizures in other types of epilepsy. For example, one study found that TMS could decrease seizure-related brain activity in patients with focal cortical dysplasia, a different type of epilepsy. Another study suggested that TMS might help reduce brain overactivity in epilepsy. However, there is no specific data provided here that directly supports TMS as an effective treatment for Rolandic Epilepsy. ^{1 2 3 4 5}

What safety data exists for transcranial magnetic stimulation in epilepsy treatment?

Repetitive transcranial magnetic stimulation (rTMS) has been studied for safety in both healthy individuals and those with epilepsy. Safety guidelines have been established since 1996, with updates in 2008 and 2021. rTMS is generally considered safe, but it carries a risk of inducing seizures, especially in epilepsy patients. A systematic review identified 46 studies on rTMS in epilepsy, noting that adverse events are generally mild, with headaches being the most common. The risk of seizures during rTMS is small, with a 1.4% crude per-subject risk, and no life-threatening seizures or status epilepticus reported. Overall, rTMS appears nearly as safe in epilepsy patients as in non-epileptic individuals, warranting further investigation as a therapy. ^{6 7 8 9 10}

Is the treatment rTMS promising for Rolandic Epilepsy?

Yes, rTMS is a promising treatment for epilepsy. Studies show it can reduce seizure frequency and is well-tolerated. It has been effective in decreasing seizures in different types of epilepsy, including temporal lobe epilepsy. ^{1 2 4 11 12}

Research Team

Fiona M Baumer, MD

Principal Investigator

Stanford University

Eligibility Criteria

This trial is for English-speaking children diagnosed with Benign Epilepsy with Centrotemporal Spikes (BECTS), also known as Rolandic Epilepsy, based on specific seizure history and EEG results. It excludes those born prematurely (<35 weeks), with serious neurological issues, focal deficits in neuro exams, or abnormal MRI findings.

Inclusion Criteria

I have been diagnosed with Rolandic Epilepsy based on my seizure history and EEG results.

English-speaking

Exclusion Criteria

You have had an MRI that showed unusual changes in your brain.

I have specific areas of weakness or loss of function.

I have had serious brain or nerve problems like seizures, severe head injuries, strokes, or diseases causing brain inflammation.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo baseline EEG measurements to assess IED frequency and brain connectivity

1 day

1 visit (in-person)

Treatment

Participants receive sham and active rTMS on 2 separate study visits to assess the impact on IED frequency and brain connectivity

2 weeks

2 visits (in-person)

Follow-up

Participants are monitored for changes in IED frequency and brain connectivity after treatment

4 weeks

Treatment Details

Interventions

• Active rTMS
• rTMS
• Sham rTMS

Trial Overview The study tests transcranial magnetic stimulation (TMS) to see if it can improve language by treating brain activity disruptions caused by BECTS. Children will receive repetitive TMS (rTMS) to potentially reduce these disruptions and change how the motor cortex connects to language regions.

Participant Groups

Group I: Children with BECTS Experimental Treatment 2 Interventions

Children will receive sham and active rTMS on 2 separate study visits separated by at least 1 week.

Active rTMS is already approved in United States, European Union for the following indications:

Approved in United States as rTMS for:

• Major Depressive Disorder (MDD)
• Obsessive-Compulsive Disorder (OCD)
• Smoking Cessation
• Chronic Pain Syndrome

Approved in European Union as rTMS for:

• Major Depressive Disorder (MDD)
• Obsessive-Compulsive Disorder (OCD)
• Chronic Pain Syndrome
• Generalized Anxiety Disorder (GAD)
• Bipolar Disorder

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Findings from Research

In a study of five patients with intractable epilepsy, three months of low-frequency repetitive transcranial magnetic stimulation (rTMS) treatment led to a significant overall reduction in mean daily number of seizures (MDNS) by 22.8%, indicating some efficacy of this treatment.

The most notable improvement was observed in a patient with focal cortical dysplasia, who experienced a 43.09% reduction in seizures, suggesting that rTMS may be particularly beneficial for patients with specific types of brain lesions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experimental therapy of epilepsy with transcranial magnetic stimulation: lack of additional benefit with prolonged treatment. Brasil-Neto, JP., de Araújo, DP., Teixeira, WA., et al.[2019]

A single session of repetitive transcranial magnetic stimulation (rTMS) effectively reduced epileptiform activity in two patients with epilepsy, as indicated by decreased brain perfusion in the targeted area after treatment.

One patient experienced a significant reduction in seizure frequency, with seizures becoming intermittent and stopping within 24 hours, while the other showed only minimal improvement, highlighting the need for further research to confirm these findings in a larger group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

rTMS reduces focal brain hyperperfusion in two patients with EPC. Graff-Guerrero, A., Gonzáles-Olvera, J., Ruiz-García, M., et al.[2019]

In a patient with medically refractory partial seizures due to focal cortical dysplasia, slow-frequency repetitive transcranial magnetic stimulation (SF-rTMS) led to a remarkable 70% reduction in seizure frequency and a 77% reduction in interictal spikes over a month of treatment.

The treatment was safe and well tolerated, with no seizures occurring during the stimulation sessions, suggesting that SF-rTMS effectively induces cortical inhibition to manage seizure activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Slow-frequency repetitive transcranial magnetic stimulation in a patient with focal cortical dysplasia. Menkes, DL., Gruenthal, M.[2019]

The pilot study involving 9 participants tested the safety and tolerability of low-frequency rTMS for treating temporal lobe epilepsy, showing that it was well-tolerated with no major adverse events reported.

While some participants experienced seizures during both active and sham stimulation, the results suggest that a larger trial is needed to further evaluate the efficacy and safety of this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary Report of the Safety and Tolerability of 1 Hz Repetitive Transcranial Magnetic Stimulation in Temporal Lobe Epilepsy. Gersner, R., Oberman, LM., Sanchez, MJ., et al.[2023]

In a study involving 8 patients with refractory epilepsy and malformations of cortical development, low-frequency repetitive transcranial magnetic stimulation (rTMS) significantly reduced epileptiform discharges in EEG by 46.4% and 42.1% at 15 and 30 days post-treatment, respectively.

The treatment also led to a notable decrease in seizure frequency, with reductions of 57.3% and 51.2% over the same time periods, indicating rTMS may be an effective therapeutic option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiepileptic effects of repetitive transcranial magnetic stimulation in patients with cortical malformations: an EEG and clinical study. Fregni, F., Thome-Souza, S., Bermpohl, F., et al.[2007]

Repetitive transcranial magnetic stimulation (rTMS) has gained popularity for its ability to modulate brain activity, but safety considerations are crucial, especially with the recent updates to safety guidelines published in 2021.

The guidelines emphasize the importance of screening for risks, monitoring for adverse events, and specific safety measures when using rTMS, particularly in patients with conditions like stroke and traumatic brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. Kim, WS., Paik, NJ.[2023]

Repetitive transcranial magnetic stimulation (rTMS) has a low risk of inducing seizures in patients with epilepsy, with a crude per subject seizure risk of only 2.9% based on an analysis of 426 subjects.

The majority of adverse events reported (18.3%) were mild, with headaches and dizziness being the most common, indicating that rTMS is generally safe and tolerable for patients with epilepsy, similar to its use in other populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of repetitive transcranial magnetic stimulation in patients with epilepsy: A systematic review. Pereira, LS., Müller, VT., da Mota Gomes, M., et al.[2022]

Transcranial magnetic stimulation (TMS) has a very low seizure risk, with only 0.08 seizures reported per 1,000 sessions, and less than 0.02 seizures per 1,000 sessions when guidelines are followed for individuals without known risk factors.

The study found that exceeding safety guidelines increases the risk of seizures, and seizures are more likely to occur during the first few TMS sessions, suggesting that TMS is generally safe when administered properly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Seizures from transcranial magnetic stimulation 2012-2016: Results of a survey of active laboratories and clinics. Lerner, AJ., Wassermann, EM., Tamir, DI.[2021]

Repetitive transcranial magnetic stimulation (rTMS) was found to be safe for a patient with an implanted subdural cortical electrode, showing no serious adverse effects during treatment.

Ex-vivo experiments indicated that rTMS caused only a slight increase in coil temperature and no displacement of the electrodes, suggesting that rTMS can be safely applied in clinical settings for patients with such implants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of repetitive transcranial magnetic stimulation in patients with implanted cortical electrodes. An ex-vivo study and report of a case. Phielipp, NM., Saha, U., Sankar, T., et al.[2019]

Repetitive transcranial magnetic stimulation (rTMS) has a low risk of inducing seizures in patients with epilepsy, with only a 1.4% incidence of seizures reported during treatment, primarily linked to low-frequency rTMS.

The majority of adverse events associated with rTMS were mild, with headaches being the most common, occurring in 9.6% of subjects, indicating that rTMS is generally safe and tolerable for individuals with epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of repetitive transcranial magnetic stimulation in patients with epilepsy: a review of the literature. Bae, EH., Schrader, LM., Machii, K., et al.[2007]

In a young adult with drug-resistant bilateral temporal lobe epilepsy, low frequency repetitive TMS (rTMS) using specially designed H-coils significantly reduced seizure frequency by 50 to 70% after three treatment courses of varying lengths (10, 15, and 30 sessions).

The rTMS treatment was well-tolerated, indicating it is a safe option for patients who do not respond to conventional epilepsy medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

H-coil repetitive transcranial magnetic stimulation for treatment of temporal lobe epilepsy: A case report. Gersner, R., Oberman, L., Sanchez, MJ., et al.[2020]

In a study involving seven adult patients with medically intractable extratemporal lobe epilepsy, low-frequency rTMS (0.9 Hz) for one week led to a reduction in seizure frequency, with complex partial seizures decreasing by 35.9%.

Patients who had a smaller difference between resting motor threshold and active motor threshold before rTMS experienced a greater reduction in complex partial seizures, suggesting that individual motor threshold measurements may help predict treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-frequency repetitive transcranial magnetic stimulation for seizure suppression in patients with extratemporal lobe epilepsy-a pilot study. Kinoshita, M., Ikeda, A., Begum, T., et al.[2014]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Experimental therapy of epilepsy with transcranial magnetic stimulation: lack of additional benefit with prolonged treatment. [2019]

2. Denmark pubmed.ncbi.nlm.nih.gov

rTMS reduces focal brain hyperperfusion in two patients with EPC. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Slow-frequency repetitive transcranial magnetic stimulation in a patient with focal cortical dysplasia. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Preliminary Report of the Safety and Tolerability of 1 Hz Repetitive Transcranial Magnetic Stimulation in Temporal Lobe Epilepsy. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Antiepileptic effects of repetitive transcranial magnetic stimulation in patients with cortical malformations: an EEG and clinical study. [2007]

6. Korea (South) pubmed.ncbi.nlm.nih.gov

Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Safety of repetitive transcranial magnetic stimulation in patients with epilepsy: A systematic review. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Seizures from transcranial magnetic stimulation 2012-2016: Results of a survey of active laboratories and clinics. [2021]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Safety of repetitive transcranial magnetic stimulation in patients with implanted cortical electrodes. An ex-vivo study and report of a case. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

Safety and tolerability of repetitive transcranial magnetic stimulation in patients with epilepsy: a review of the literature. [2007]

11. United States pubmed.ncbi.nlm.nih.gov

H-coil repetitive transcranial magnetic stimulation for treatment of temporal lobe epilepsy: A case report. [2020]

12. England pubmed.ncbi.nlm.nih.gov

Low-frequency repetitive transcranial magnetic stimulation for seizure suppression in patients with extratemporal lobe epilepsy-a pilot study. [2014]