Noninvasive Imaging for Epilepsy

Recruiting at 1 trial location

Overseen By Aaliyah M HamidullahThiam

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)

Must not be taking: Benzodiazepines, Barbiturates, Antidepressants, others

Disqualifiers: Pregnancy, Claustrophobia, Psychiatric disorders, others

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

Compensation: Varies

Number of Visits: 2

700 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Objectives: The overall study objective is to compare the sensitivities and specificities of morphometric analysis techniques using structural MRI images based on pre- and postsurgical localization of epileptic foci in patients undergoing presurgical evaluation for medically refractory epilepsy. To carry out these analyses, we aim to establish an age-stratified normative imaging database using healthy volunteers. Additional objectives are to identify abnormal networks in these patients using resting state fMRI/EEG and MEG/EEG, and to use language and memory fMRI tasks to examine the effects of epileptogenic zones and surgery on cognitive function and the networks associated with these functions. Study population: 300 adults and children (age 8 and older) with uncontrolled focal epilepsy, and 200 age-stratified healthy volunteers. Design: A retrospective and prospective natural history study. Research procedures for patients in this study include neuropsychological testing and 1-4 MRI sessions during presurgical evaluation and an additional 1-3 MRI sessions and neuropsychological testing approximately 12 months post-operatively. Research testing (such as research neuropsychological tests or MRI scanning sequences) will be done during a visit for clinical testing whenever possible, likely reducing the number of required visits. Patients will also have optional MEG and 7T structural imaging. Data will also be obtained from patients who have already undergone epilepsy surgery if they had procedures as outlined in the protocol and are willing to share the data. Healthy volunteers will receive a subset of the pre-operative procedures for patients, requiring at least 3 visits. In order to ensure adequate data acquisition, subjects may be re-scanned up to three times for the portions of the study in which they participated, possibly requiring additional visits. Outcome measures: The main outcomes will be establishment of normative values for morphometric analysis methods in age-stratified normal controls, and comparison of the sensitivity and specificity of these measures to pre- and postsurgical localization of the epileptogenic zone. Secondary outcome measures will include determination of the sensitivity and specificity of source localization using MEG/EEG and resting state fMRI/EEG, and to evaluate changes in activation during rest, as well as language and memory fMRI tasks in patients pre- and postsurgically, to examine the effects of epileptogenic zones and surgery on cognitive function and the networks underlying these functions.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop your current medications. However, healthy volunteers must not have used centrally acting medications like benzodiazepines, barbiturates, antidepressants, beta-blockers, or drugs for epilepsy or migraine in the past 6 weeks.

Is MEG safe for use in humans?

Magnetoencephalography (MEG) is a noninvasive imaging technique used in epilepsy evaluation and is generally considered safe for humans, including children and infants, as it measures brain activity without any direct contact or radiation exposure. ^{1 2 3 4 5}

How is the treatment using MEG and MRI for epilepsy different from other treatments?

This treatment is unique because it uses magnetoencephalography (MEG) combined with magnetic resonance imaging (MRI) to noninvasively map brain activity and locate epileptic areas with high precision, unlike traditional methods that often require invasive procedures. ^{2 6 7 8 9}

What data supports the effectiveness of the treatment MEG and MRI for epilepsy?

Research shows that MEG, often combined with MRI, is effective in accurately locating the sources of epileptic activity in the brain. This helps doctors decide if surgery is a good option for patients with epilepsy, especially when other tests don't show clear results. ^{2 5 6 10 11}

Who Is on the Research Team?

Sara K Inati, M.D.

Principal Investigator

National Institute of Neurological Disorders and Stroke (NINDS)

Are You a Good Fit for This Trial?

This trial is for adults and children aged 8 or older with uncontrolled focal epilepsy, who are being evaluated for or have had epilepsy surgery. Participants must be able to consent themselves or through a guardian and cooperate with MRI scans without anesthesia.

Inclusion Criteria

I am 8 years old or older and being evaluated for epilepsy surgery.

Documentation of focal epilepsy based on MRI, EEG, and/or ictal semiology

I can give consent or have someone who can legally consent for me.

Exclusion Criteria

Not able or willing to give consent or do not have an appropriate surrogate who can provide consent

I do not have major health issues affecting my brain or nerves.

I haven't taken any central nervous system medications in the last 6 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Presurgical Evaluation

Participants undergo neuropsychological testing and 1-4 MRI sessions to evaluate epileptic foci

Varies

1-4 visits (in-person)

Post-operative Evaluation

Participants undergo additional 1-3 MRI sessions and neuropsychological testing approximately 12 months after surgery

12 months

1-3 visits (in-person)

Follow-up

Participants are monitored for changes in cognitive function and network activity post-surgery

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• MEG
• MRI
• Noninvasive Pre-surgical Evaluation

Trial Overview The study aims to improve the detection of epileptic foci using MRI before and after surgery in patients with refractory epilepsy. It also involves creating a database from healthy volunteers for comparison, plus additional brain imaging (MEG) and cognitive testing.

How Is the Trial Designed?

Group I: healthy volunteers Experimental Treatment 2 Interventions

healthy volunteers

Group II: Patients Experimental Treatment 2 Interventions

Patients

MEG is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Magnetoencephalography for:

• Epilepsy diagnosis
• Presurgical evaluation

Approved in European Union as Magnetoencephalography for:

• Epilepsy diagnosis
• Presurgical evaluation
• Neurological disorders

Approved in Canada as Magnetoencephalography for:

• Epilepsy diagnosis
• Presurgical evaluation

Approved in Japan as Magnetoencephalography for:

• Epilepsy diagnosis
• Presurgical evaluation
• Neurological disorders

Who Is Running the Clinical Trial?

National Institute of Neurological Disorders and Stroke (NINDS)

Lead Sponsor

Trials

1,403

Recruited

655,000+

Published Research Related to This Trial

Magnetoencephalography (MEG) shows promise as a noninvasive tool for localizing epilepsy, but the current evidence does not strongly support its effectiveness in predicting seizure-free outcomes after surgery, based on a systematic review of 17 studies.

The review highlighted significant variability in sensitivity and specificity of MEG results, indicating that more research is needed to establish a clear relationship between MEG localization and successful surgical resection in epilepsy patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review on MEG and its use in the presurgical evaluation of localization-related epilepsy. Lau, M., Yam, D., Burneo, JG.[2018]

Magnetoencephalography (MEG) plays a crucial role in the clinical evaluation of patients with pharmacoresistant epilepsy, helping to determine who is eligible for epilepsy surgery.

The primary benefit of MEG is that it increases the number of patients who can proceed to surgery, but it should not be used as a reason to deny surgical options to any patient.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetoencephalography adds to the surgical evaluation process. Stefan, H., Rampp, S., Knowlton, RC.[2011]

Magnetoencephalography (MEG) demonstrated a high sensitivity of 90% in detecting interictal epileptiform activity in infants with pharmacoresistant epilepsy, effectively identifying seizure foci even when EEG showed generalized dysfunction in 80% of cases.

In a cohort of 18 infants who underwent surgery, 72% achieved seizure freedom, particularly those with focal spike volumes identified by MEG, highlighting its critical role in the presurgical evaluation and decision-making process for infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetoencephalographic Recordings in Infants: A Retrospective Analysis of Seizure-Focus Yield and Postsurgical Outcomes. Garcia-Tarodo, S., Funke, M., Caballero, L., et al.[2018]

Magnetoencephalography (MEG) has become a routine clinical tool for accurately localizing sources of epileptic spikes, both during seizures and between them, showing high accuracy compared to traditional methods like intracranial EEG.

Despite its effectiveness, MEG faces challenges in detecting complex or deep brain sources, but it remains crucial for evaluating the significance of abnormalities found in other imaging techniques, enhancing noninvasive approaches to epilepsy surgery evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetoencephalography in epilepsy. Knowlton, RC., Shih, J.[2007]

Magnetoencephalography (MEG) is now routinely used in clinical practice to improve the presurgical evaluation of patients with epilepsy and brain tumors, helping to localize brain activity accurately.

Studies indicate that using MEG to localize epileptic discharges can lead to better postsurgical outcomes for epilepsy patients, highlighting its importance in treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical applications of magnetoencephalography. Stufflebeam, SM., Tanaka, N., Ahlfors, SP.[2023]

Magnetoencephalography (MEG) is an advanced imaging technique that effectively localizes epileptiform activity in children, showing good correlation with invasive monitoring methods during surgery.

MEG can enhance surgical planning for pediatric epilepsy by accurately mapping critical brain functions and guiding neurosurgeons in selecting the safest approach for treatment, particularly in complex cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of magnetoencephalography in pediatric epilepsy surgery. Grondin, R., Chuang, S., Otsubo, H., et al.[2022]

Pediatric magnetoencephalography (MEG) is a noninvasive technique that can significantly enhance clinical practice and research for infants and young children, particularly in understanding brain activity.

Current pediatric MEG systems are limited, but they hold promise for improving the diagnosis and treatment of conditions like drug-resistant epilepsy, highlighting a need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pediatric Magnetoencephalography in Clinical Practice and Research. Papadelis, C., Chen, YH.[2021]

Magnetoencephalography (MEG) is a non-invasive imaging technique that captures the brain's electrical activity through magnetic fields, and when combined with MRI, it forms Magnetic Source Imaging (MSI) which is useful for evaluating epilepsy.

MSI is increasingly utilized in the presurgical assessment of patients with refractory partial epilepsy, helping to accurately localize brain areas associated with epileptic discharges, which can guide surgical planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contribution of magnetic source imaging to the presurgical work-up of patients with refractory partial epilepsy. De Tiège, X., Op de Beeck, M., Bourguignon, M., et al.[2009]

Magnetoencephalography (MEG) is now routinely used in clinical settings to accurately localize sources of epileptic spikes, both during seizures and in between them, providing a reliable tool for epilepsy evaluation.

MEG helps to assess the significance of abnormalities found in other imaging techniques, making it a crucial noninvasive method for evaluating candidates for epilepsy surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetoencephalography: clinical application in epilepsy. Knowlton, RC.[2019]

Magnetoencephalography (MEG) is a noninvasive imaging technique that allows for precise localization of brain activity, making it the preferred method for mapping functional areas in the brain, especially in epilepsy patients.

MEG can effectively identify the irritative zone in epilepsy, map critical language areas, and assess language development in children, thus enhancing the evaluation process for epilepsy surgery and other neurological conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetoencephalography (MEG) and magnetic source imaging (MSI). Wheless, JW., Castillo, E., Maggio, V., et al.[2019]

Magnetoencephalography (MEG) is highly effective for presurgical evaluation in epilepsy due to its excellent spatio-temporal resolution, particularly in analyzing interictal spikes.

Combining MEG results with detailed clinical symptomatology enhances the identification of epileptic foci, highlighting the need for integrated epilepsy diagnosis and treatment teams in hospitals to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Magnetoencephalography analysis of epileptic foci]. Imai, K.[2018]

Citations

1. Netherlands pubmed.ncbi.nlm.nih.gov

A systematic review on MEG and its use in the presurgical evaluation of localization-related epilepsy. [2018]

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

Magnetoencephalography adds to the surgical evaluation process. [2011]

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

Magnetoencephalographic Recordings in Infants: A Retrospective Analysis of Seizure-Focus Yield and Postsurgical Outcomes. [2018]

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

Magnetoencephalography in epilepsy. [2007]

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

Clinical applications of magnetoencephalography. [2023]

6. Germany pubmed.ncbi.nlm.nih.gov

The role of magnetoencephalography in pediatric epilepsy surgery. [2022]

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

Pediatric Magnetoencephalography in Clinical Practice and Research. [2021]

8. Belgium pubmed.ncbi.nlm.nih.gov

Contribution of magnetic source imaging to the presurgical work-up of patients with refractory partial epilepsy. [2009]

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

Magnetoencephalography: clinical application in epilepsy. [2019]

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

Magnetoencephalography (MEG) and magnetic source imaging (MSI). [2019]

11. Japan pubmed.ncbi.nlm.nih.gov

[Magnetoencephalography analysis of epileptic foci]. [2018]