Focused Ultrasound Thalamotomy for Epilepsy and Anxiety

Overseen By Anne-Marie Duchemin

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Ohio State University

Must not be taking: Anticoagulants, Antiplatelets

Disqualifiers: Low seizure frequency, Generalized epilepsy, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 1 day

10 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the feasibility, safety, and effects on anxiety of high intensity focused ultrasound ablation (FUSA) in patients suffering from treatment-refractory focal epilepsy and anxiety. FUSA is a non-invasive neurosurgical procedure that uses ultrasound waves, sent directly through the scalp and skull, to precisely target small abnormal areas of the brain. For this study, the targeted area of the brain is the anterior nucleus of the thalamus. This brain region may cause seizures and may also be involved in anxiety. The study will test if FUSA is safe and tolerated, and if it reduces anxiety and brain response to threat in patients with anxiety receiving the procedure for partial-onset epilepsy that is resistant to medications.

Do I have to stop taking my current medications for the trial?

The trial requires that you maintain a stable dosage of your current anti-epileptic and psychotropic/psychoactive medications for 3 months before and after enrollment. So, you should not stop taking your current medications.

What data supports the idea that Focused Ultrasound Thalamotomy for Epilepsy and Anxiety is an effective treatment?

The available research does not provide specific data on the effectiveness of Focused Ultrasound Thalamotomy for Epilepsy and Anxiety. Instead, it focuses on its use for treating tremor conditions, such as essential tremor. The studies show that this treatment is safe and effective for tremors, as it is incisionless and can be performed under general anesthesia. However, there is no direct evidence in the provided research about its effectiveness for epilepsy and anxiety. ^{1 2 3 4 5}

What safety data exists for focused ultrasound thalamotomy?

The safety of focused ultrasound thalamotomy, also known as MRgFUS, has been evaluated in various studies. These studies have demonstrated its safety and efficacy, particularly for conditions like essential tremor. Postoperative MR imaging is used to assess lesion location and extent, although there is no consensus on the frequency of imaging. Factors affecting the procedure's efficiency, such as patient-specific and procedure-related factors, have been studied. The treatment is typically performed with the patient awake, but it has also been done under general anesthesia. Intraoperative imaging can accurately detect lesional findings, and the accumulated thermal dose can predict lesion size, aiding in treatment planning. ^{1 2 3 5 6}

Is Magnetic Resonance Imaging-guided Focused Ultrasound Ablation (MRgFUSA) a promising treatment for epilepsy and anxiety?

Yes, MRgFUSA is a promising treatment because it is a non-invasive method that uses focused ultrasound waves to target specific areas in the brain, potentially helping with conditions like epilepsy and anxiety. It has been shown to be effective in treating tremors and other conditions, suggesting it could be beneficial for epilepsy and anxiety as well. ^{1 2 3 4 6}

Research Team

Kinh Luan Phan, MD

Principal Investigator

Ohio State University

Timothy Lucas, MD

Principal Investigator

Ohio State University

Eligibility Criteria

This trial is for adults with focal epilepsy and moderate to severe anxiety who haven't responded well to treatments. They must have had a stable medication dose for 3 months, experience at least 3 seizures per month, and be able to follow the study's procedures. People can't join if they have low seizure frequency, certain other neurological conditions, recent substance abuse, or are pregnant.

Inclusion Criteria

Ability to comply with all testing, follow-ups, and study appointments and protocols

Previous seizure work-up within 12 months of enrollment date to include: A. Home EEG or EMU video EEG or intracranial EEG. B. High definition MRI imaging/PET imaging. C. Baseline neuropsychological assessment, which includes the Wechsler Advanced Clinical Solutions - Test of Premorbid Functioning (TOPF)

I have had 3 or more seizures a month in the last 3 months.

Exclusion Criteria

Active suicidal ideation current and past 30 days

I am currently on dialysis.

IQ score of <70 on the Wechsler Advanced Clinical Solutions - Test of Premorbid Functioning (TOPF), measured as part of screening neuropsychological assessment

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants undergo Unilateral Magnetic Resonance Imaging-guided Focused Ultrasound Ablation (MRgFUSA) of the anterior nucleus of the thalamus

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including neuroimaging and neuropsychological assessments

12 months

Multiple visits at day 1, week 1, month 1, month 3, month 6, and month 12

Long-term Follow-up

Participants' anxiety and seizure frequency are monitored using various assessments

12 months

Treatment Details

Interventions

• Magnetic Resonance Imaging-guided Focused Ultrasound Ablation (MRgFUSA)

Trial Overview The trial tests MR-guided Focused Ultrasound Ablation (MRgFUSA) on the anterior nucleus of the thalamus in patients with treatment-resistant focal epilepsy and anxiety. It aims to see if this non-invasive procedure is safe and reduces both seizures and anxiety symptoms.

Participant Groups

Group I: Intervention Experimental Treatment 1 Intervention

Unilateral Magnetic Resonance Imaging-guided Focused Ultrasound Ablation (MRgFUSA) of the anterior nucleus of the thalamus (ATN)

Magnetic Resonance Imaging-guided Focused Ultrasound Ablation (MRgFUSA) is already approved in United States for the following indications:

Approved in United States as MRgFUSA for:

• Essential Tremor
• Tremor-dominant Parkinson's disease
• Internal Globus Pallidus for Parkinson's disease dyskinesia

Who Is Running the Clinical Trial?

Ohio State University

Lead Sponsor

Trials

891

Recruited

2,659,000+

Findings from Research

This study reports the first successful case of MRgFUS thalamotomy performed under general anesthesia, demonstrating its safety and feasibility for patients unable to undergo the procedure while awake due to medical conditions.

The patient experienced a significant 89% improvement in tremor postoperatively, confirming the efficacy of the treatment even without intraprocedural neurological assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic Resonance-Guided Focused Ultrasound Thalamotomy for Essential Tremor Under General Anesthesia: Technical Note. Mensah-Brown, KG., Yang, AI., Hitti, FL., et al.[2022]

Intraoperative neuroimaging during transcranial MR-guided focused ultrasound (tcMRgFUS) thalamotomy effectively visualizes lesional zones, with zone I (coagulation necrosis) seen in 68% of patients immediately after treatment and significantly more at 48 hours, indicating its utility in monitoring treatment progress.

The size of the lesions, particularly zones I and II, increased significantly from the intraoperative assessment to the 48-hour follow-up, and these sizes correlated well with sonication parameters, suggesting that intraoperative imaging can guide treatment effectiveness and adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative imaging findings in transcranial MR imaging-guided focused ultrasound treatment at 1.5T may accurately detect typical lesional findings correlated with sonication parameters. Gagliardo, C., Cannella, R., Quarrella, C., et al.[2021]

In a study of 215 patients undergoing MRgFUS thalamotomy for essential tremor, lesions were visible in all patients immediately after the procedure, but by 3 months, only 54.7% had detectable lesions, which were significantly smaller (83.6% reduction).

The study found that while certain sonication parameters influenced the persistence of lesions, the visibility of these lesions did not correlate with improvements in tremor symptoms, indicating that lesion size alone may not predict clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Longitudinal MR imaging after unilateral MR-guided focused ultrasound thalamotomy: clinical and radiological correlation. Blitz, SE., Chua, MMJ., Ng, P., et al.[2023]

In a study involving 6 patients with various types of tremors, MRI-guided focused ultrasound (MRgFUS) targeting the ventro-intermedius nucleus (Vim) resulted in a significant reduction in tremor scores, with improvements sustained for up to 6 months.

While MRgFUS is a promising incision-free treatment for tremors other than essential tremor, some patients experienced transient and persistent side effects, highlighting the need for further research on its safety and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MRI-guided focused ultrasound thalamotomy in non-ET tremor syndromes. Fasano, A., Llinas, M., Munhoz, RP., et al.[2022]

In a study of 92 patients undergoing MRgFUS thalamotomy for tremor, the efficiency of heating (HE) was significantly affected by the skull density ratio (SDR), with lower SDR leading to diminished HE and less effective temperature elevation during treatment.

The findings indicate that in 11% of patients with an SDR below 0.45, the heating efficiency was insufficient to achieve the necessary temperature for effective treatment, highlighting the importance of patient-specific anatomical factors in the success of MRgFUS procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-specific effects on sonication heating efficiency during magnetic resonance-guided focused ultrasound thalamotomy. Yang, AI., Hitti, FL., Alabi, OO., et al.[2021]

In a study involving 36 patients with essential tremor, the accumulated thermal dose (ATD) during MR-guided focused ultrasound (MRgFUS) thalamotomy was found to correlate with the size of brain lesions, helping to predict treatment outcomes.

The optimal ATD values for predicting lesion size were identified as 100 and 200 cumulative equivalent minutes at 43°C, providing valuable insights for determining effective treatment endpoints in future MRgFUS procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predicting lesion size by accumulated thermal dose in MR-guided focused ultrasound for essential tremor. Huang, Y., Lipsman, N., Schwartz, ML., et al.[2019]

References

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

Magnetic Resonance-Guided Focused Ultrasound Thalamotomy for Essential Tremor Under General Anesthesia: Technical Note. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

Intraoperative imaging findings in transcranial MR imaging-guided focused ultrasound treatment at 1.5T may accurately detect typical lesional findings correlated with sonication parameters. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Longitudinal MR imaging after unilateral MR-guided focused ultrasound thalamotomy: clinical and radiological correlation. [2023]

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

MRI-guided focused ultrasound thalamotomy in non-ET tremor syndromes. [2022]

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

Patient-specific effects on sonication heating efficiency during magnetic resonance-guided focused ultrasound thalamotomy. [2021]

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

Predicting lesion size by accumulated thermal dose in MR-guided focused ultrasound for essential tremor. [2019]