Focused Ultrasound Pallidotomy for Cerebral Palsy

Overseen By Saige Teti

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Children's National Research Institute

Must be taking: Anti-dystonic medications

Must not be taking: Anticoagulants

Disqualifiers: Primary dystonia, Severe spasticity, 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

Will I have to stop taking my current medications?

The trial requires that your anti-dystonic medication has been stable for the last 30 days, so you may not need to stop taking it. However, if you are on anticoagulant medications, you will need to discontinue them during the perioperative period (time around surgery).

What data supports the effectiveness of the treatment Focused Ultrasound Pallidotomy for Cerebral Palsy?

Research shows that MR-guided focused ultrasound pallidotomy has been effective in improving motor symptoms in Parkinson's disease, with significant improvements in movement scores and quality of life. This suggests potential benefits for similar neurological conditions, like cerebral palsy, although direct evidence for cerebral palsy is not yet available. ^{1 2 3 4 5}

Is MR-guided focused ultrasound pallidotomy generally safe for humans?

MR-guided focused ultrasound pallidotomy has been studied for conditions like Parkinson's disease, showing mostly mild and temporary side effects such as headaches and nausea. However, there was a case of skull bone injury, indicating that while generally safe, there are potential risks that need further investigation. ^{1 2 5 6 7}

How is the treatment Focused Ultrasound Pallidotomy unique for cerebral palsy?

Focused Ultrasound Pallidotomy is unique because it uses sound waves to create precise lesions in the brain without needing surgery, which is different from traditional surgical methods. This non-invasive approach is guided by MRI, allowing for targeted treatment with potentially fewer side effects. ^{1 2 3 5 8}

What is the purpose of this trial?

The primary objective of the proposed study is to evaluate the safety of ExAblate Transcranial MRgFUS as a tool for creating bilateral or unilateral lesions in the globus pallidus (GPi) in patients with treatment-refractory secondary dystonia due to dyskinetic cerebral palsy

Research Team

Chima Oluigbo, MD

Principal Investigator

Children's National Hospital, Washington, DC

Eligibility Criteria

This trial is for young individuals aged 8-22 with secondary dystonia due to cerebral palsy caused by perinatal hypoxic injury. They should have tried other medications without enough benefit and be considered for pallidotomy or GPi-DBS by their doctor. Participants need stable medication for the last month, an intact globus pallidus on MRI, no severe skeletal deformations requiring surgery, and must consent to the study.

Inclusion Criteria

I, or my child, understand the study and agree to participate.

I do not have severe bone deformities that require urgent surgery.

I, or my legal guardian, understand the study and have given written consent.

Exclusion Criteria

I don't have brain conditions that prevent DBS surgery.

Minimum head circumference < 49cm

Skull Density Ratio (SDR) <0.40

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo Focused Ultrasound Pallidotomy to create lesions in the globus pallidus (GPi)

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness, including assessments of quality of life, motor development, and cognition

24 months

Regular visits over 2 years

Long-term follow-up

Continued monitoring of adverse events and quality of life impacts

Additional 6 months

Treatment Details

Interventions

• Focused Ultrasound Pallidotomy

Trial Overview The trial tests ExAblate Transcranial MRgFUS's safety in creating lesions within a brain region called the globus pallidus. This non-invasive procedure aims to alleviate treatment-resistant dystonic movements in patients with dyskinetic cerebral palsy.

Participant Groups

Group I: Focused Ultrasound Pallidotomy Experimental Treatment 1 Intervention

Pediatric and young adult patients between ages of 8 and 22 years with pharmaco-resistant secondary dystonia due to dyskinetic cerebral palsy who have Focused Ultrasound Pallidotomy

Focused Ultrasound Pallidotomy is already approved in United States for the following indications:

Approved in United States as ExAblate Neuro for:

• Essential Tremor
• Tremor-predominant Parkinson's disease

Who Is Running the Clinical Trial?

Children's National Research Institute

Lead Sponsor

Trials

227

Recruited

258,000+

Findings from Research

Unilateral MR-guided focused ultrasound (MRgFUS) pallidotomy significantly improved dyskinesia scores in 20 patients with Parkinson's disease, showing a 59% reduction in the Unified Dyskinesia Rating Scale (UDysRS) scores at 3 months, which was sustained at 12 months.

The procedure was safe, with mostly mild and transient adverse events, and no serious adverse effects as defined by US FDA criteria, indicating that MRgFUS could be a viable treatment option for managing motor fluctuations in Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MR-guided focused ultrasound pallidotomy for Parkinson's disease: safety and feasibility. Eisenberg, HM., Krishna, V., Elias, WJ., et al.[2023]

In a study of 30 patients treated with MR-guided focused ultrasound (MRgFUS) for movement disorders, 7 patients developed new skull lesions after treatment, although all were asymptomatic and lesions were not visible immediately after the procedure.

The study found that higher energy levels applied during the MRgFUS procedure were associated with the development of skull lesions, suggesting that local skull properties may influence the risk of such lesions, warranting further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Skull bone marrow injury caused by MR-guided focused ultrasound for cerebral functional procedures. Schwartz, ML., Yeung, R., Huang, Y., et al.[2019]

The study presents an optimized strategy for performing pallidothalamic tractotomy (PTT) using MR-guided focused ultrasound (MRgFUS) in patients with chronic therapy-resistant Parkinson's disease, based on detailed histological analysis of 6 human brain hemispheres.

A standardized target coverage for PTT was established, involving 5 to 7 preplanned lesion sub-units, which enhances the precision and effectiveness of the procedure while maintaining thermal dose control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anatomical and Technical Reappraisal of the Pallidothalamic Tractotomy With the Incisionless Transcranial MR-Guided Focused Ultrasound. A Technical Note. Gallay, MN., Moser, D., Federau, C., et al.[2020]

In a study involving 10 patients with early-stage tremor-dominant Parkinson's disease who underwent MRgFUS thalamotomy, the procedure was found to effectively reduce tremors without the need to increase dopaminergic medication over 6 months.

In contrast, a control group of 20 patients on standard dopaminergic therapy showed a significant increase in their medication dosage, highlighting the potential of MRgFUS as a beneficial alternative treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic Resonance-Guided Focused Ultrasound Thalamotomy May Spare Dopaminergic Therapy in Early-Stage Tremor-Dominant Parkinson's Disease: A Pilot Study. Golfrè Andreasi, N., Cilia, R., Romito, LM., et al.[2023]

Unilateral MR-guided focused ultrasound (MRgFUS) pallidotomy showed significant efficacy in reducing dyskinesia in patients with Parkinson's disease, with improvements of 32.2% in motor symptoms and 52.7% in dyskinesia scores at the 6-month follow-up.

The procedure was successfully performed in 80% of patients, with no persistent side effects reported, although one patient experienced an unusual side effect, highlighting the need for further research to address potential technical limitations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and limits of magnetic resonance-guided focused ultrasound pallidotomy for Parkinson's disease: a Phase I clinical trial. Jung, NY., Park, CK., Kim, M., et al.[2019]

Magnetic resonance imaging-guided focused ultrasound (MRgFUS) shows potential as a treatment for medication-resistant Parkinson's disease, with 10 out of 11 studies reporting a decline in motor symptoms as measured by UPDRS-III scores, and four studies indicating significant improvements in quality of life.

Most adverse events related to MRgFUS were mild and temporary, suggesting that the treatment is generally safe; however, the overall evidence is limited, highlighting the need for more rigorous studies with larger participant groups and longer follow-up periods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of magnetic resonance imaging-guided focused ultrasound neurosurgery for Parkinson's disease: a systematic review. Xu, Y., He, Q., Wang, M., et al.[2021]

In a study of 123 patients undergoing magnetic resonance-guided focused ultrasound for tremor, those with lower skull density ratios were three times more likely to experience moderate or severe headaches, suggesting that tailored analgesic prophylaxis may be beneficial for these patients.

Women were found to have a significantly higher likelihood of experiencing nausea compared to men, with four times the odds, indicating a need for gender-specific considerations in managing side effects during the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Factors Associated with Headache and Nausea During Magnetic Resonance-Guided Focused Ultrasound for Tremor. Cacho-Asenjo, E., Honorato-Cia, C., Nuñez-Cordoba, JM., et al.[2022]

MR-guided focused ultrasound (MRgFUS) thalamotomy is more efficient than pallidotomy for creating therapeutic lesions, requiring significantly less energy to reach the necessary temperature for treatment (5.7 kJ for thalamotomy vs. 10.9 kJ for pallidotomy).

The study found that the location of the target within the brain affects treatment efficiency, with thalamotomy (located centrally) achieving higher maximum temperatures and requiring less energy compared to pallidotomy (off-center), which may influence patient selection for these procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Technical Comparison of Treatment Efficiency of Magnetic Resonance-Guided Focused Ultrasound Thalamotomy and Pallidotomy in Skull Density Ratio-Matched Patient Cohorts. Ahmed, AK., Guo, S., Kelm, N., et al.[2022]

References

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

MR-guided focused ultrasound pallidotomy for Parkinson's disease: safety and feasibility. [2023]

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

Skull bone marrow injury caused by MR-guided focused ultrasound for cerebral functional procedures. [2019]

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

Anatomical and Technical Reappraisal of the Pallidothalamic Tractotomy With the Incisionless Transcranial MR-Guided Focused Ultrasound. A Technical Note. [2020]

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

Magnetic Resonance-Guided Focused Ultrasound Thalamotomy May Spare Dopaminergic Therapy in Early-Stage Tremor-Dominant Parkinson's Disease: A Pilot Study. [2023]

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

The efficacy and limits of magnetic resonance-guided focused ultrasound pallidotomy for Parkinson's disease: a Phase I clinical trial. [2019]

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

Safety and efficacy of magnetic resonance imaging-guided focused ultrasound neurosurgery for Parkinson's disease: a systematic review. [2021]

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

Factors Associated with Headache and Nausea During Magnetic Resonance-Guided Focused Ultrasound for Tremor. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Technical Comparison of Treatment Efficiency of Magnetic Resonance-Guided Focused Ultrasound Thalamotomy and Pallidotomy in Skull Density Ratio-Matched Patient Cohorts. [2022]