Neural Mechanism of Theta-Burst Transcranial Magnetic Stimulation (TBS) for Freezing of Gait

Study Overview
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Brief Summary
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To investigate the treatment effect of Theta-burst Transcranial Magnetic Stimulation (TBS) on patients with freezing of gait (FOG) and the underlying neural mechanism.

Detailed Description
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This was a open-label clinical trial. Forty patients with FOG were treated with TBS for 5 days. Each patient was given a high-dose iTBS of 9000 pulses/day for each target to stimulate the lower extremity motor area and dorsolateral prefrontal lobe respectively. The stimulation sequence of the two targets was randomized among subjects, and the stimulation sequence within the subjects remained unchanged throughout the course of treatment for 5 consecutive days (18000 pulses/day, 90,000 pulses in total). Before the TBS treatment, the Freezing of Gait Questionnaire, the Timed up and go test, the Standing Start 180° Turning Test, the Unified Parkinson's Disease Rating Scale, and the Non-motor Symptom Scale, the Pittsburgh sleep quality index were obtained by a trained investigator to assess baseline severity. The patients had receiving a battery measure of neuropsychological tests(mini-mental state examination, Montreal cognitive assessment, digital span test, verbal fluency test, Hamilton depression/anxiety scale) and magnetic resonance imaging (MRI) scan in multimodalities, electroencephalography (EEG) record, and biological specimens (blood, urine, etc.). In the second day after the last treatment, all the tests, MRI, EEG and biological specimens were reassessed. Patients were instructed to focus their answers on the past 5 days. The clinical symptom and cognition of participants were followed in one month and two month after the last treatment.

Official Title
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Neural Mechanism of Theta-Burst Transcranial Magnetic Stimulation (TBS) for Freezing of Gait

Conditions
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Transcranial Magnetic Stimulation, Freezing of Gait

Intervention / Treatment
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* Device: transcranial magnetic stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diagnosis of FOG with expertise in movement disorders. the score of item 3 of the FOG questionnaire ≥1. ongoing treatment with a stable dose of any medication for 2 months. 40 years of age or older. Exclusion Criteria: a history of addiction, psychiatric disorders, or neurological diseases other than PD. focal brain lesions on T1-/T2-weighted fluid-attenuated inversion recovery images. anti-PD medication adjustments during rTMS treatment. history of substance abuse within the past 6 months. nonremovable metal objects in or around the head. previously received rTMS treatment. prior history of seizure or history in first-degree relatives.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Real Stimulation<br>The continuous theta burst stimulation (iTBS) protocol lasted 10 min and consisted of 1800 pulses. In the iTBS session, this 10min protocol was repeated for ten times (18000 pulses in total) separated by 50 min breaks (controlled by a stopwatch). MRI dataset should be acquired before the first iTBS session and after the last iTBS session. | Device: transcranial magnetic stimulation<br>* The stimulations were performed by MagStim Rapid2.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Standing-Start 180° Turn Test (SS-180) | The participants walk for a distance of five meters from a sitting position and come back to the chair after turning 180° around a traffic cone in a 0.7 m × 0.7 m target box.The time during the 180° turn (SS180) are measured. The time is recorded in seconds, and the longer the time, the more severe the symptoms | changes from baseline to 1-week post-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The timed up and go test (TUG) | The participants walk for a distance of five meters from a sitting position and come back to the chair after turning 180° around a traffic cone in a 0.7 m × 0.7 m target box .The time during the whole course are measured. The time is recorded in seconds, and the longer the time, the more severe the symptoms | changes from baseline to 1-week post-treatment | 
| The Freezing of Gait Questionnaire (FOGQ) | This is an very common clinical motor estimating scale for evaluating FOG. 6 items and each item scored between 0 and 4 points (24 scores in total). A higher score indicates more severe symptoms | changes from baseline to 1-week post-treatment | 
| Unified Parkinson's Disease Rating Scale III (UPDRSIII) | This is an very common clinical motor estimating scale, 14 items and 108' in total. Higher scores indicate worse symptoms. | changes from baseline to 1-week post-treatment | 
| Non-motor symptoms questionnaire (NMSS) | This is a very common clinical scale with nine domains (30 items). Each item was scored on severity range from 1 to 3 and frequency range from 1 to 4. Higher scores indicate worse symptoms. | changes from baseline to 1-week post-treatment | 
| HAMD (Hamilton Depression Scale) | This scale was compiled by Hamilton in 1960, is the most common clinical to assess Depression Scale. In this study, 17 versions were selected, and there were 17 questions. The subjects were assessed for their depression in the past week. Each question scored between 0 and 4 points.Higher scores indicate more depressive symptoms. | changes from baseline to 1-week post-treatment | 
| HAMA (Hamilton Anxiety Scale) | This scale was compiled by Hamilton in 1959.It was one of the most commonly used scales in psychiatric clinic, including 14 items. It is often used in clinical diagnosis and degree classification of anxiety disorder. The subjects were assessed for their anxiety in the past week. Each question scored between 0 and 4 points. The higher the score, the more symptoms of anxiety. | changes from baseline to 1-week post-treatment | 
| Mini Mental State Exam (MMSE) | The commonly used scale of cognitive function test can reflect the mental state and the degree of cognitive dysfunction of the subjects comprehensively, accurately and rapidly. A total of 30 questions, each correct answer 1 point | changes from baseline to 1-week post-treatment | 
| Montreal Cognitive Assessment (MoCA) | The changes in MoCA will constitute assess response to rTMS the secondary research outcome measure used to.MoCA was developed by Nasreddine et al. based on clinical experience and reference to the MMSE cognitive items and scores, and the final version was finalized in November 2004. We adopted a localized version (Mandarin version#includes 2 alternative versions) in line with the Chinese cultural background.It includes 11 inspection items in 8 cognitive fields, including visual structure skills, executive function, naming, attention and calculation, language, abstract thinking, memory, and orientation. With a total score of 30 or more than 26, it is normal. Anyone who has been education for less than 12 years will need to add one point to his final score. The final score of the higher the better, and we hope the subjects' scores will improve after treatment. | changes from baseline to 1-week post-treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Transcranial Magnetic Stimulation, Freezing of Gait