MRgFUS for Writer's Cramp

(FUS Dystonia Trial)

Overseen By Najme Hosseini

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Maryland, Baltimore

Must not be taking: Anticoagulants, Antiplatelets

Disqualifiers: Generalized dystonia, Severe psychiatric disorder, Pregnancy, Severe hypertension, 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: 1

Duration: 1 day

10 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to assess the safety and effectiveness of MRI-guided focused ultrasound (MRgFUS) for treating task specific focal hand dystonias (TSFD). TSFD is a type of dystonia that affects hand movements during specific tasks such as writing, playing instruments or typing, often causing involuntarily movements or cramping.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are on anticoagulant or antiplatelet medications.

What data supports the effectiveness of the treatment MRgFUS Pallidotomy for Writer's Cramp?

MR-guided focused ultrasound (MRgFUS) has been shown to be a safe and effective treatment for reducing tremors in conditions like Parkinson's disease and essential tremor, suggesting it may also help with similar movement disorders like Writer's Cramp. ^{1 2 3 4 5}

Is MR-guided focused ultrasound (MRgFUS) generally safe for humans?

MR-guided focused ultrasound (MRgFUS) has been used in treatments for conditions like Parkinson's disease and essential tremor. Some studies report that it is generally safe, but there have been cases of side effects such as skull lesions, functional tremors, and temporary adverse events. More research and long-term follow-up are needed to fully understand its safety. ^{1 4 5 6 7}

How is MRgFUS Pallidotomy treatment different from other treatments for Writer's Cramp?

MRgFUS Pallidotomy is unique because it uses focused ultrasound waves guided by MRI to target and destroy specific brain tissue without the need for invasive surgery, offering a non-invasive alternative to traditional surgical methods. ^{8 9 10 11 12}

Eligibility Criteria

This trial is for individuals with task specific focal hand dystonias (TSFD), which causes involuntary movements or cramping of the hands during activities like writing or playing instruments. Participants must meet certain health criteria to be eligible.

Inclusion Criteria

I am between 22 and 74 years old.

I have had symptoms for more than 6 months.

Pallidotomy is feasible based on evaluation of imaging studies

Exclusion Criteria

Patient with contraindications to MRI such as severe claustrophobia and metallic implants incompatible with MRI

Inability to provide informed consent, for example due to underlying cognitive impairment or aphasia

I have muscle contractions affecting multiple body areas.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo MR guided focused ultrasound thalamotomy targeting the globus pallidus internus (GPi) using the ExAblate Transcranial system

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments including adverse events and changes in dystonia intensity and quality of life

6 months

Multiple visits (in-person and virtual)

Treatment Details

Interventions

• MRgFUS Pallidotomy

Trial Overview The study is testing the safety and effectiveness of a non-invasive procedure called MRgFUS Pallidotomy, which uses MRI-guided focused ultrasound to target brain areas involved in TSFD.

Participant Groups

Group I: ExAblate Transcranial treatment Experimental Treatment 1 Intervention

The ExAblate Transcranial system will be used to destroy a small cluster of cells that may be causing the study participant's pain . The ExAblate uses ultrasound to heat a small spot in the brain called globus pallidus internus(GPi). Ultrasound passes through the skin and skull and into the brain to focus on this particular spot.

MRgFUS Pallidotomy is already approved in United States, European Union for the following indications:

Approved in United States as MRgFUS Pallidotomy for:

• Parkinson's disease
• Essential tremor
• Dyskinesias
• Task specific focal hand dystonias (TSFD)

Approved in European Union as MRgFUS Pallidotomy for:

• Parkinson's disease
• Essential tremor
• Dyskinesias

Who Is Running the Clinical Trial?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

Focused Ultrasound Foundation

Collaborator

Trials

18

Recruited

460+

InSightec

Industry Sponsor

Trials

92

Recruited

3,800+

Dr. Maurice R. Ferré

InSightec

Chief Executive Officer

MD

Dr. Arjun Desai

InSightec

Chief Medical Officer

MD

Findings from Research

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]

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 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 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]

This case study describes the first instance of a functional tremor developing in a 71-year-old man after a successful MR-guided focused ultrasound thalamotomy (MRgFUS) for essential tremor, highlighting a potential complication of this treatment.

Electrophysiological studies confirmed the presence of both essential tremor and a functional tremor, emphasizing the importance of recognizing such complications to prevent unnecessary additional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional tremor developing after successful MRI-guided focused ultrasound thalamotomy for essential tremor. Alshimemeri, S., Vargas-Méndez, D., Chen, R., et al.[2022]

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 guided focused ultrasound (MRgFUS) thalamotomy is a safe and effective treatment for medication-resistant essential tremors, improving various scores related to tremors and quality of life.

However, there can be significant side effects, such as new-onset parkinsonian features and speech changes, which may arise from unintended effects on surrounding brain structures during the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemi-parkinsonism and return of essential tremors after MRgFUS thalamotomy: Case report and review of procedural complications affecting ventral thalamic nuclei. Varma-Doyle, AV., Villemarette-Pittman, NR., Copeland, BJ.[2021]

In a study of 34 patients undergoing microvascular decompression (MVD) surgery for hemifacial spasm, the rhomboid lip was encountered in 26.5% of cases, indicating its significance during the procedure.

The rhomboid lip is rarely visible on preoperative MR images, but careful dissection during surgery is crucial to improve visualization of cranial nerve VII and prevent potential postoperative complications, such as dysphagia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Importance of awareness of the rhomboid lip in microvascular decompression surgery for hemifacial spasm. Nakahara, Y., Matsushima, T., Hiraishi, T., et al.[2013]

In a study of 102 patients undergoing awake craniotomy for brain lesions near the primary motor area, factors like preoperative paresis and tumor type significantly influenced the risk of worsened motor function after surgery.

Successful awake surgery and avoiding intraoperative complications are crucial for preventing deterioration of motor function one month post-surgery, especially in patients with tumors that compress motor pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Awake craniotomy for brain lesions within and near the primary motor area: A retrospective analysis of factors associated with worsened paresis in 102 consecutive patients. Shinoura, N., Midorikawa, A., Yamada, R., et al.[2022]

In a study of 14 patients with unilateral hemifacial spasm (HS) and 20 controls, MRI and MRA revealed that neurovascular contact at the facial nerve root exit zone was significantly more common in patients (12 out of 14) compared to controls (4 out of 20), suggesting that this contact may be a key factor in causing HS.

The use of MRI and MRA as non-invasive diagnostic tools is recommended for evaluating hemifacial spasm, as they can effectively visualize the relationship between cranial nerves and adjacent blood vessels, supporting the hypothesis that local irritation of the facial nerve is a likely cause of the condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic resonance imaging and angiography in hemifacial spasm. Felber, S., Birbamer, G., Aichner, F., et al.[2019]

The study identified a new MRI finding called the Prevedello Sign (PS) that significantly aids in diagnosing neurovascular conflict (NVC) in patients with hemifacial spasm (HFS), showing a sensitivity of 94.2% and specificity of 91.4%.

When combined with standard MRI evaluations, the PS increased the sensitivity of detecting NVC to over 99%, enhancing surgical success rates without adding risks or costs for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A New Finding on Magnetic Resonance Imaging for Diagnosis of Hemifacial Spasm with High Accuracy and Interobserver Correlation. Finger, G., Wu, KC., Vignolles-Jeong, J., et al.[2023]

Pre-operative magnetic resonance tomographic angiography (MRTA) is significantly more effective than routine MRI in identifying offending vessels in patients with medically intractable hemifacial spasm (HFS), with a positive identification rate of 82.8%.

Microvascular decompression (MVD) surgery achieved a high relief rate of 91.2% in 215 patients, with a low recurrence rate of only 3.5% after more than two years of follow-up, indicating it is a safe and effective treatment option for HFS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Microvascular decompression for hemifacial spasm: experience of 215 cases]. Zhao, W., Shen, J., Pu, C.[2006]

References

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

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

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

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

3. 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]

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

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

5. England pubmed.ncbi.nlm.nih.gov

Functional tremor developing after successful MRI-guided focused ultrasound thalamotomy for essential tremor. [2022]

6. 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]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Hemi-parkinsonism and return of essential tremors after MRgFUS thalamotomy: Case report and review of procedural complications affecting ventral thalamic nuclei. [2021]

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

Importance of awareness of the rhomboid lip in microvascular decompression surgery for hemifacial spasm. [2013]

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

Awake craniotomy for brain lesions within and near the primary motor area: A retrospective analysis of factors associated with worsened paresis in 102 consecutive patients. [2022]

10. Germany pubmed.ncbi.nlm.nih.gov

Magnetic resonance imaging and angiography in hemifacial spasm. [2019]

11. Switzerland pubmed.ncbi.nlm.nih.gov

A New Finding on Magnetic Resonance Imaging for Diagnosis of Hemifacial Spasm with High Accuracy and Interobserver Correlation. [2023]

12. China pubmed.ncbi.nlm.nih.gov

[Microvascular decompression for hemifacial spasm: experience of 215 cases]. [2006]