TMS for Temporal Lobe Epilepsy

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Chicago

Must be taking: Antiepileptic drugs

Must not be taking: Antipsychotics, Psychostimulants

Disqualifiers: Neurological illness, Children, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 4 weeks

34 Participants Needed

Trial Summary

What is the purpose of this trial?

The aim of this pilot study is to understand hippocampal network function in mesial temporal lobe epilepsy (MTLE) and to test whether transcranial magnetic stimulation (TMS) targeting the network of the hippocampus can change hippocampal-dependent memory task performance and epileptic activity in people with (MTLE). Positive findings would implicate the hippocampal network as a source of these typical primary MTLE symptoms. Subjects with a primary diagnosis of MTLE will be enrolled in a non-randomized, non-blinded pilot experiment to test target engagement and preliminary efficacy of a novel neurostimulation approach targeting the hippocampal network. At baseline, subjects will undergo neurocognitive testing for hippocampal-dependent memory and functional magnetic resonance imagining (fMRI) neuroimaging assessment of brain structure and task-dependent activity. They will also receive scalp-electroencephalography (EEG) to measure interictal epileptiform discharge (IED) frequency at baseline, and will complete a seizure diary for one month. They will then receive high-frequency repetitive TMS targeting an area of parieto-occipital cortex defined based on fMRI connectivity with the hippocampus measured at baseline. The baseline assessments will then be repeated, using an alternate form of the memory test. The investigators will analyze changes from baseline in memory task performance, fMRI activity of the hippocampal network, IED frequency, and reported seizure frequency.

Will I have to stop taking my current medications?

The trial requires that participants have a stable antiepileptic drug regimen, meaning your current epilepsy medications should not change for at least one month before joining the study. However, if you are taking other medications that affect cognition, you may not be eligible to participate.

What data supports the effectiveness of the treatment Transcranial Magnetic Stimulation (TMS) for Temporal Lobe Epilepsy?

While the research provided does not directly address TMS for Temporal Lobe Epilepsy, it highlights the effectiveness of other minimally invasive treatments like stereotactic laser ablation and deep brain stimulation (DBS) for drug-resistant epilepsy. These treatments show promise in managing seizures, suggesting that non-invasive approaches like TMS could potentially offer benefits as well. ^{1 2 3 4 5}

Is TMS generally safe for humans?

TMS is generally considered safe, but it can cause seizures, which are rare and usually self-limiting. In patients with epilepsy, the risk of seizures is small, and other mild side effects like headaches are similar to those seen in treatments for other conditions. ^{6 7 8 9 10}

How does TMS treatment for temporal lobe epilepsy differ from other treatments?

TMS (Transcranial Magnetic Stimulation) is unique because it uses magnetic fields to target deep brain areas, like those involved in temporal lobe epilepsy, without surgery. Unlike medications or invasive surgeries, TMS is non-invasive and can reduce seizure frequency significantly, as shown in studies with patients who did not respond to drugs. ^{3 4 11 12 13}

Research Team

Joel Voss, PhD

Principal Investigator

University of Chicago

Eligibility Criteria

This trial is for individuals with a primary diagnosis of mesial temporal lobe epilepsy (MTLE). Participants should be able to undergo neurocognitive testing, fMRI scans, and EEG monitoring. They must also keep a seizure diary for one month. Specific inclusion and exclusion criteria details are not provided.

Inclusion Criteria

I am a native English speaker.

My epilepsy medication has been the same for at least a month.

My vision is normal or corrected to normal.

Exclusion Criteria

I am not on any cognition-impairing drugs except for anticonvulsants for MTLE.

I am under 18 years old.

I have a neurological condition that is not mesial temporal lobe epilepsy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Subjects undergo neurocognitive testing, fMRI, and EEG to assess baseline hippocampal network function and epileptic activity

1 day

1 visit (in-person)

Pre-Treatment Monitoring

Subjects complete a daily seizure diary for one month to track baseline seizure frequency

4 weeks

Treatment

Subjects receive up to 5 sessions of high-frequency repetitive TMS targeting the hippocampal network

4 weeks

5 visits (in-person)

Post-Treatment Assessment

Subjects undergo repeat neurocognitive testing, fMRI, and EEG to assess changes from baseline

1 day

1 visit (in-person)

Follow-up

Subjects continue to complete a daily seizure diary for 30 days to track changes in seizure frequency post-treatment

4 weeks

Treatment Details

Interventions

• Transcranial Magnetic Stimulation (TMS)

Trial Overview The study tests if transcranial magnetic stimulation (TMS) can affect memory performance and epileptic activity in MTLE patients by targeting the hippocampal network. It involves baseline assessments, TMS sessions, and follow-up evaluations to measure changes in memory task performance and brain activity.

Participant Groups

Group I: Experiment 1 Experimental Treatment 1 Intervention

Subjects will be tested for baseline performance on a memory task while in an MRI scanner and with scalp EEG. Subjects will then receive multiple sessions, of repetitive transcranial magnetic stimulation. Post-treatment, baseline assessments will be repeated. Overall study period per subject: 2 months

Transcranial Magnetic Stimulation (TMS) is already approved in United States, European Union for the following indications:

Approved in United States as Transcranial Magnetic Stimulation (TMS) for:

• Major Depressive Disorder (MDD)
• Obsessive-Compulsive Disorder (OCD)
• Migraine Headache Symptoms

Approved in European Union as Transcranial Magnetic Stimulation (TMS) for:

• Major Depressive Disorder (MDD)
• Obsessive-Compulsive Disorder (OCD)

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Findings from Research

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) 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]

Single-pulse transcranial magnetic stimulation (sTMS) has been shown to be a low-risk technique with minimal adverse events, making it a promising option for diagnosing and treating neurological and psychiatric conditions, including migraines.

Extensive clinical experience over two decades indicates that sTMS does not cause harm to brain tissue or neurophysiological function, supporting its safety as a nonpharmacologic treatment for acute migraine headaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation for migraine: a safety review. Dodick, DW., Schembri, CT., Helmuth, M., et al.[2010]

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]

References

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

Stereotactic laser ablation of amygdala and hippocampus using a Leksell stereotactic frame. [2019]

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

In search of optimal DBS paradigms to treat epilepsy: bilateral versus unilateral hippocampal stimulation in a rat model for temporal lobe epilepsy. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Comparison of therapeutic effects between selective amygdalohippocampectomy and anterior temporal lobectomy for the treatment of temporal lobe epilepsy: a meta-analysis. [2014]

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

Minimally invasive surgical approaches for temporal lobe epilepsy. [2019]

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

Anterior nucleus of the thalamus deep brain stimulation vs temporal lobe responsive neurostimulation for temporal lobe epilepsy. [2023]

6. Netherlands pubmed.ncbi.nlm.nih.gov

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

7. Brazil pubmed.ncbi.nlm.nih.gov

[Transcranial magnetic stimulation: review of accidental seizures]. [2019]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Transcranial Magnetic Stimulation (TMS) Safety with Respect to Seizures: A Literature Review. [2020]

9. 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]

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

Transcranial magnetic stimulation for migraine: a safety review. [2010]

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

The cortical excitability profile of temporal lobe epilepsy. [2013]

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

The Effect of Epilepsy and Antiepileptic Drugs on Cortical Motor Excitability in Patients With Temporal Lobe Epilepsy. [2021]