High-Intensity Focused Ultrasonic Ablation of the Centromedian Thalamic Nucleus for Treatment of Medically Refractory Generalized Epilepsy in Patients Ages 18 Years to 89 Years (HIFU for MRGE)

High-Intensity Focused Ultrasonic Ablation of the Centromedian Thalamic Nucleus for Treatment of Medically Refractory Generalized Epilepsy

The purpose of this study is to find out if magnetic resonance (MRI)-guided high-intensity focused ultrasound (HIFU) is safe and effective for treating medically refractory generalized epilepsy. HIFU is a procedure that delivers ultrasonic waves to brain regions with great precision to remove tissue that may cause problems. HIFU is approved by the Federal Drug Administration (FDA) for treating patients with essential tremor.

This study aims to find out if HIFU can safely reduce seizure burden in patients with medically refractory generalized epilepsy (MRGE) using metrics commonly used in other treatments for epilepsy, and by the change in frequency of convulsive (generalized tonic-clonic) seizures before and after the intervention.

Study Overview

• Status: Not yet recruiting
• Conditions: Idiopathic Generalized Epilepsy
• Intervention / Treatment: Device: Intervention 1; Device: Intervention 2

Detailed Description

The primary purpose of this study is to evaluate the safety of thalamotomy targeting the centromedian thalamic nucleus (CMN) using magnetic resonance-guided high-intensity focused ultrasound (HIFU), an incisionless, ablative procedure that selectively delivers ultrasonic waves to brain regions with submillimeter precision, which is already FDA-approved for thalamotomy in essential tremor and in practice at many institutions, including that of the investigators. The proposed study aims to determine if ablation of CMN using HIFU can safely reduce generalized seizure burden in patients with medically refractory generalized epilepsy (MRGE) using success metrics commonly used in interventions for epilepsy and by the change in frequency of convulsive (generalized tonic-clonic) seizures before and after the intervention.

Current literature suggests that thalamotomy with HIFU for essential tremor produces minimal and generally transient side effects, while targeted lesioning of CMN with other modalities such as radiofrequency ablation (RFA) produces similarly transient side effects in patients with MRGE. No mortality associated with treatment was reported in any study. Furthermore, the benefits for this patient population from RFA or from deep brain stimulation (DBS) of CMN ranged from 50-98% reduction in generalized seizures as long as 36 months post-operatively. Thus, we hypothesize that HIFU ablation of CMN will safely produce a similar durable reduction in generalized seizure burden for patients with MRGE.

In the proposed study, patients will be evaluated for three months pre-intervention and followed for one year after Intervention 1. The same schedule will be followed by subjects who proceed to receive Intervention 2.

Seizure freedom will be defined according to the International League Against Epilepsy (ILAE) outcome classification scale. The ILAE outcome scale includes six classes of outcome: Class 1 = seizure free; Class 2 = auras only; Class 3 = one to three seizure days/year and auras; Class 4 = four seizure days/year to 50% reduction in baseline and auras; Class 5 = <50% reduction in baseline number of seizure days to 100% increase in baseline number of seizure days and auras; Class 6 = >100% increase in baseline number of seizure days and auras. Only patients classified as ILAE Class 1 or Class 2 will be considered seizure-free.

This is a proof-of-concept interventional study whose primary aims are as follows:

Primary Aim 1: To characterize the safety of bilateral CMN ablation using HIFU in terms of both somatic and neuropsychological adverse events.

Primary Aim 2: To determine the efficacy of bilateral CMN ablation using HIFU in reducing generalized seizure burden and effect on interictal Electroencephalogram (EEG) anomalies.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Michael McGehee, MS; Phone Number: 971-509-4932; Email: nsgclinicalresearch@ohsu.edu

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
      • Principal Investigator: Ahmed Raslan, MD
      • Contact: Michael T McGehee, MS; Phone Number: 503-494-4988; Email: nsgclinicalresearch@ohsu.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Ages 18 years to 89 years.
2. Adult males or females, non-pregnant, on reliable contraceptive regimen as appropriate.
3. Patient and legal representative as appropriate capable of signing written informed consent, completing electronic seizure diary, participating in questionnaires.
4. EEG features of generalized epilepsy performed within two years of enrollment with EEG anomalies not explained by contributory medical history; CT and/or MRI within the last ten years demonstrating no anatomic etiology of epilepsy.
5. MRGE, defined as persistent generalized tonic-clonic seizures, with or without concomitant absence, myoclonic, or focal seizures, despite compliance with at least two anti-seizure medications at therapeutic doses, with at least two generalized tonic-clonic seizures per month in the three months prior to HIFU procedure; must be willing to continue medication regimen during the duration of participation in the study.
6. Patient has not already undergone surgical implantation of RNS, VNS, DBS, or any other device used for management of MRGE that is not compatible with 3 Tesla MRI.

Exclusion Criteria:

1. 1. Pregnancy.
2. Unable or unwilling to comply with inclusion criteria as described.

3. Prior disqualifying medical or surgical history:

   1. Patients with advanced kidney disease or on dialysis
   2. Patients with unstable cardiac status:

   I. Unstable angina pectoris on medication II. Subjects with documented myocardial infarction within six months of protocol entry III. Significant congestive heart failure defined with ejection fraction < 40 IV. Subjects with unstable ventricular arrhythmias V. Subjects with atrial arrhythmias that are not rate-controlled c. Patients with severe hypertension (diastolic BP>100 on medication) d. Patients exhibiting any behavior consistent with ethanol or substance abuse e. Patients with history of abnormal bleeding, hemorrhage, and/or coagulopathy f. Patients receiving anticoagulant or drugs known to increase risk of hemorrhage within one month of focused ultrasound procedure g. Patients with cerebrovascular disease h. Patients with brain tumors i. Patients who are not able or unwilling to tolerate the required prolonged stationary position during treatment. The average treatment time (the time from the first scan to allocate transducer position and ending with the last energy delivery) is 1:56 ± 0.41 hrs (Min: 0.48 hrs, Max: 5:54 hrs) j. Patients with unstable psychiatric disease, uncontrolled depressive symptoms, psychosis, delusions, hallucinations, or suicidal ideation

4. Patients who are not candidates for HIFU.

   a. Patients who have an Overall Skull Density Ratio of 0.40 (±0.05) or less as calculated from the screening CT

5. Patients with standard contraindications for MRI such as non-MRI compatible implanted devices including cardiac pacemakers, size limitations, etc.
6. Inability to tolerate MRI without premedication, sedation, or anesthesia.
7. Known intolerance or allergies to MRI contrast agent (e.g. Gadolinium or Magnevist)
8. History of craniotomy or other prior cranial procedure that would render phase correction with CT inaccurate.

9. Subjects with risk factors for intraoperative or postoperative bleeding:

   1. Platelet count less than 100,00 per cubic millimeter
   2. INR coagulation studies exceeding local institution laboratory standards
   3. Documented coagulopathy
10. Subject with life-threatening systemic disease that include and not limited to the following: HIV, liver failure, blood dyscrasias, etc.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention 1; Ten patients will undergo unilateral HIFU treatment of the dominant hemisphere CMN (Intervention 1). Safety follow-up visits will take place at 2-weeks, 1-month, 3-months, 6-months, 9-months, and 1-year post-treatment to assess for persistent clinically relevant adverse events (AEs) and any AEs related to HIFU treatment. A seizure severity assessment will also be performed at these follow-up visits. Seizure freedom will be defined according to the ILAE classification, with only patients in ILAE classes 1 or 2 considered seizure-free. At the 1-year follow-up visit, patients who have not experienced persistent clinically relevant AEs related to HIFU treatment, and who are not seizure-free according to the ILAE classification, will proceed to second-side HIFU treatment of the CMN (Intervention 2) after an additional three-month pre-second-side evaluation. Patients who are seizure-free according to the ILAE classification after unilateral treatment, or who develop clinically relevant ad	Device: Intervention 1; HIFU ablation of dominant-hemisphere centromedian thalamic nucleus (CMN), or dominant seizure activity hemisphere
Experimental: Intervention 2; At the 1-year follow-up visit (for Intervention 1 - unilateral HIFU treatment of CMN), patients who have not experienced persistent clinically relevant AEs related to HIFU treatment, and who are not seizure-free according to the ILAE classification, will proceed to second-side HIFU treatment of the CMN (Intervention 2) after an additional three-month pre-second-side evaluation. Patients who are seizure-free according to the ILAE classification after unilateral treatment, or who develop clinically relevant adverse events (AEs) and any AEs related to HIFU treatment, will not undergo second-side treatment and will exit the study after the 1-year follow-up visit.	Device: Intervention 2; HIFU ablation of contralateral centromedian thalamic nucleus (CMN)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Aim 1	Number of participants with device-related or procedure-related serious adverse events (SAEs) such as deaths, hospitalizations, or life-threatening events as assessed by CTCAE v5.0.	From enrollment to 1 year following treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Aim 2	Number of participants with decreased seizure frequency or severity as assessed according to the ILAE classification.	From enrollment to 1 year following treatment

Collaborators and Investigators

• Sponsor: Oregon Health and Science University
• Collaborators: InSightec
• Investigators: Principal Investigator: Ahmed Raslan, MD, Oregon Health and Science University

Publications and helpful links

Helpful Links

• Centromedian Nucleus of the Thalamus Deep Brain Stimulation for Genetic Generalized Epilepsy: A Case Report and Review of Literature
• Radiofrequency ablation of the centromedian thalamic nucleus in the treatment of drug-resistant epilepsy
• Centromedian thalamic nucleus with or without anterior thalamic nucleus deep brain stimulation for epilepsy in children and adults: A retrospective case series
• The centromedian nucleus: Anatomy, physiology, and clinical implications.
• Optimally targeting the centromedian nucleus of the thalamus for generalized epilepsy: A meta-analysis
• Imaging the Centromedian Thalamic Nucleus Using Quantitative Susceptibility Mapping.
• Ultrasound Blood-Brain Barrier Opening and Aducanumab in Alzheimer's Disease.
• RNS System NAUTILUS Study (NAUTILUS)
• Teratogenic potential of third-generation antiepileptic drugs: Current status and research needs.
• Network Substrates of Centromedian Nucleus Deep Brain Stimulation in Generalized Pharmacoresistant Epilepsy
• Centromedian Nucleus and Epilepsy
• Centromedian thalamic neuromodulation for the treatment of idiopathic generalized epilepsy

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2027
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): June 1, 2031

Study Registration Dates

• First Submitted: August 10, 2026
• First Submitted That Met QC Criteria: August 31, 2026
• First Posted (Actual): September 4, 2026

Study Record Updates

• Last Update Posted (Actual): September 4, 2026
• Last Update Submitted That Met QC Criteria: August 31, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: epilepsy; generalized epilepsy; High Intensity Focused Ultrasound; HIFU; seizure
• Additional Relevant MeSH Terms: Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Epilepsy; Seizures; Epilepsy, Generalized; Epilepsy, Idiopathic Generalized
• Other Study ID Numbers: STUDY00027836

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD will be shared via secure GitHub folder, which will be provided at time of manuscript submission.
• IPD Sharing Time Frame: Data will be uploaded for each subject following each respective 90 days follow-up until study conclusion.
• IPD Sharing Access Criteria: Principal Investigator and IRB-approved study team members will have access to this information and are able to share with others via password protected link.
• IPD Sharing Supporting Information Type: ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes