MRI to Study Deep Brain Stimulation Effects in Neurodegenerative Disease

Overseen by Andres Lozano

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: University Health Network, Toronto

Disqualifiers: Cognitive impairments, Speech deficits, others

Stay on Your Current Meds

No Placebo Group

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial studies the effects of a treatment using electrical impulses on patients with various neurological and psychiatric conditions. Researchers will use advanced imaging techniques to understand how this treatment affects brain function and structure. This method has been used for over twenty years to treat movement disorders and is a promising treatment for other conditions.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of this treatment?

Deep brain stimulation (DBS) is shown to improve motor function in advanced Parkinson's disease and is being explored for treating dementia. MRI helps in precisely targeting brain areas for DBS, potentially enhancing its effectiveness. ^{1 2 3 4 5}

Is Deep Brain Stimulation (DBS) generally safe for humans?

Deep Brain Stimulation (DBS) is generally considered safe, but it can have complications like infection (2-9%), bleeding (1-4%), and seizures (1-3%). MRI scans on DBS patients have been performed safely without causing harm, although specific safety guidelines should be followed. ^{6 7 8 9 10}

How is deep brain stimulation different from other treatments for neurodegenerative diseases?

Deep brain stimulation (DBS) is unique because it involves surgically implanting electrodes in specific brain areas to modulate brain activity, unlike other treatments that might use medication or non-invasive methods. This approach allows for a highly individualized treatment plan, especially when using advanced imaging techniques like ultrahigh-field MRI to precisely target the brain regions involved. ^{1 2 3 5 11}

Research Team

Andres Lozano

Principal Investigator

University Health Network, Toronto

Eligibility Criteria

This trial is for adults aged 18-85 with neurodegenerative diseases who are undergoing or have undergone deep brain stimulation (DBS) electrode implantation. They must understand the study and consent to participate, acknowledging they won't directly benefit from it. Those with serious cognitive impairments or communication issues, such as non-English speakers or those with speech deficits, cannot join.

Inclusion Criteria

Participants must be able to understand the purpose of this research and must sign the informed consent form

Participants must understand that the role of this research is to enhance our understanding of brain functioning and that he/she will not directly or indirectly benefit from the study

I am scheduled for or have had DBS electrode implantation.

Exclusion Criteria

Participants who are unable to effectively or efficiently communicate, for example patients suffering from speech deficits (dysarthria, aphasia) or are non-English speaking

I am able to understand and consent to participate in the study.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-operative Assessment

Patients undergo pre-operative MRI scans to assess brain structure and function before DBS implantation

3 months

Multiple visits for MRI scans

Post-operative Follow-up

Patients undergo fMRI scanning with different DBS settings to aid in programming and assess therapeutic effects

1 year

Regular visits for fMRI and clinical assessments

Long-term Follow-up

Participants are monitored for safety and effectiveness of DBS therapy over an extended period

1 year

Treatment Details

Interventions

• Deep Brain Stimulation (DBS) (Procedure)
• fMRI (Other)

Trial Overview The trial uses advanced MRI technology to perform functional magnetic resonance imaging (fMRI) on patients with DBS implants. The goal is to observe how DBS affects brain function and explore if fMRI can help improve clinical practices for these patients.

Participant Groups

Group I: fMRI-based programming Experimental Treatment 1 Intervention

DBS patients will undergo fMRI scanning while on different stimulation settings. The results will be fed to the programming clinician (movement disorder neurologist) to aid the conventional programming process at the clinician's discretion.

Deep Brain Stimulation (DBS) is already approved in Canada for the following indications:

Approved in Canada as Deep Brain Stimulation for:

• Parkinson's disease
• Essential tremor
• Dystonia

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Dr. Brad Wouters

University Health Network, Toronto

Chief Medical Officer since 2020

MD from University of Toronto

Dr. Kevin Smith

University Health Network, Toronto

Chief Executive Officer since 2018

Professor at McMaster University and University of Toronto

Findings from Research

Deep brain stimulation (DBS) has been explored as a treatment for dementia, with three studies focusing on its effects, including one on fornix DBS for Alzheimer's disease and two on nucleus basalis of Meynert for Alzheimer's and Parkinson's disease dementia.

Current evidence for the effectiveness of DBS in treating dementia is still preliminary and limited, indicating a need for further research to understand its potential clinical benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for the treatment of Alzheimer disease and dementias. Laxton, AW., Lozano, AM.[2022]

Deep brain stimulation (DBS) for advanced Parkinson's disease, using Multiple Sequences Image Fusion (MuSIF) for accurate targeting, led to a significant reduction of 76% in L-dopa equivalent daily dose after 3 months.

Patients experienced a 50% reduction in dyskinesias and a 45% decrease in motor fluctuations, demonstrating the efficacy of the combined imaging techniques in improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiple sequential image-fusion and direct MRI localisation of the subthalamic nucleus for deep brain stimulation. Rampini, PM., Locatelli, M., Alimehmeti, R., et al.[2017]

Deep brain stimulation (DBS) is a surgical treatment for neurological disorders that can be enhanced by using ultrahigh-field (UHF) MRI for planning, which allows for greater precision in targeting areas of the brain.

Using UHF MRI improves the clinical efficacy of DBS by enabling a more individualized approach to treatment, potentially leading to better outcomes for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultra High Field MRI-Guided Deep Brain Stimulation. Forstmann, BU., Isaacs, BR., Temel, Y.[2018]

In a study of 40 Parkinson's disease patients undergoing subthalamic deep brain stimulation (STN-DBS), 45% reported significant improvement in sleep quality at 6 months, although this improvement was not statistically significant at 12 months.

The most common benefits included better overall sleep quality and maintenance, but some patients experienced new-onset daytime sleepiness, indicating that while STN-DBS can improve sleep, the effects can vary widely among individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in Parkinson's disease sleep symptoms and daytime somnolence after bilateral subthalamic deep brain stimulation in Parkinson's disease. Kharkar, S., Ellenbogen, JR., Samuel, M., et al.[2020]

The study established an effective MRI protocol using MPRAGE T1W, FSE T2W, and ME-GRE sequences for clear visualization of brain targets and electrodes in patients undergoing deep brain stimulation (DBS), involving 29 patients and healthy controls.

Despite the severe imaging artifacts caused by DBS electrodes, these artifacts can be beneficial for accurately locating the electrodes, enhancing the reliability of postoperative imaging assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imaging patients pre and post deep brain stimulation: Localization of the electrodes and their targets. Li, Y., Buch, S., He, N., et al.[2021]

A study using the Deep Brain Stimulation Brain Tissue Network's database found no adverse clinical or pathological effects from performing 1.5 T MRI scans on patients with implanted DBS devices, suggesting that MRI is relatively safe for these patients.

Further examination of post-mortem brains with DBS leads exposed to prolonged 3T MRI also showed no evidence of heat-related damage, supporting the safety of higher field strength MRI in DBS patients under current guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot study of human brain tissue post-magnetic resonance imaging: information from the National Deep Brain Stimulation Brain Tissue Network (DBS-BTN). Ullman, M., Vedam-Mai, V., Krock, N., et al.[2011]

A study involving 249 deep brain stimulation (DBS) patients who underwent 445 MRI sessions found no adverse events related to the MRI scans, indicating that brain MRI at 1.5 Tesla is safe for DBS patients.

The study highlighted that the specific absorption rates (SAR) during scans were higher than current product labeling allows, suggesting a need for updated safety guidelines for MRI use in DBS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of brain MRI after deep brain stimulation hardware implantation. Nazzaro, JM., Lyons, KE., Wetzel, LH., et al.[2010]

Deep brain stimulation is an effective treatment for movement disorders, involving an implanted electrode and pulse generator, but its mechanisms of action are not fully understood and were developed without extensive preclinical safety studies.

Complication rates for deep brain stimulation can exceed 25%, with 4-6% of patients experiencing permanent neurological issues, highlighting the need for better understanding of adverse events and safer stimulation methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety considerations for deep brain stimulation: review and analysis. Grill, WM.[2007]

Deep Brain Stimulation (DBS) for Parkinson's disease can lead to rare complications, such as an intracranial abscess, as demonstrated in a case involving a 59-year-old male who developed significant inflammation and required multiple surgeries after the procedure.

Despite the complications, the patient's Parkinson's symptoms improved after the abscess was surgically drained, suggesting that the abscess may have inadvertently provided some therapeutic benefit similar to a subthalomotomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracerebral abscess: a rare complication of Deep Brain Stimulation. Brandão, E., Rosas, MJ., Abreu, P., et al.[2013]

Deep brain stimulation (DBS) is generally safe and effective for treating movement disorders, but this case highlights a rare complication: a cerebral infarction following DBS surgery in a patient with cervical dystonia.

The ischemia may have been caused by high-amplitude microstimulation, potentially leading to small-vessel vasospasm, indicating that while DBS is beneficial, careful monitoring of stimulation parameters is crucial to avoid such complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cerebral ischemia related to globus pallidus internus stimulation for cervical dystonia. Kang, DW., Kim, HY., Chang, JW.[2011]

Using a body-transmit coil for cranial MRI in patients with deep brain stimulation (DBS) devices can lead to increased electrode heating, but remains within safe limits at 1.5T, with temperature increases below 1°C under controlled conditions.

At 3T, cranial MRI can exceed safety guidelines for heating, indicating that careful monitoring and specific protocols are essential for safely conducting fMRI studies in DBS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Safety of Using Body-Transmit MRI in Patients with Implanted Deep Brain Stimulation Devices. Kahan, J., Papadaki, A., White, M., et al.[2022]

References

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

Deep brain stimulation for the treatment of Alzheimer disease and dementias. [2022]

2. Italy pubmed.ncbi.nlm.nih.gov

Multiple sequential image-fusion and direct MRI localisation of the subthalamic nucleus for deep brain stimulation. [2017]

3. England pubmed.ncbi.nlm.nih.gov

Ultra High Field MRI-Guided Deep Brain Stimulation. [2018]

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

Changes in Parkinson's disease sleep symptoms and daytime somnolence after bilateral subthalamic deep brain stimulation in Parkinson's disease. [2020]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Imaging patients pre and post deep brain stimulation: Localization of the electrodes and their targets. [2021]

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

A pilot study of human brain tissue post-magnetic resonance imaging: information from the National Deep Brain Stimulation Brain Tissue Network (DBS-BTN). [2011]

7. England pubmed.ncbi.nlm.nih.gov

Use of brain MRI after deep brain stimulation hardware implantation. [2010]

8. England pubmed.ncbi.nlm.nih.gov

Safety considerations for deep brain stimulation: review and analysis. [2007]

9. Spain pubmed.ncbi.nlm.nih.gov

Intracerebral abscess: a rare complication of Deep Brain Stimulation. [2013]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Cerebral ischemia related to globus pallidus internus stimulation for cervical dystonia. [2011]

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

The Safety of Using Body-Transmit MRI in Patients with Implanted Deep Brain Stimulation Devices. [2022]