Functional Movement Disorder
Conditions
Keywords
Functional Movement Disorders, Transcranial Magnetic Stimulation (TMS), iTBS, Repetitive Transcranial Magnetic Stimulation, Neuroimaging, Conversion Disorder
Brief summary
Background: Functional movement disorders (FMD) involve involuntary movements that are not due to a recognized neurological or medical cause. FMD can cause major disability. Researchers want to learn more to create better treatments for FMD. Objective: To test whether non-invasive brain stimulation using transcranial magnetic stimulation (TMS) improves FMD symptoms. Eligibility: People between the ages of 18 and 80 who have been diagnosed with FMD by a neurologist. Design: Participants will be randomly assigned to one of two groups. One group is an active brain stimulation group and the other is a sham brain stimulation group. Participants will have a baseline visit. This will include: Neurological exam Questionnaires Urine test Brain MRI: Participants will lie in a machine that takes pictures of the body. They will be asked to respond to images on a screen while in the scanner. Within 2 weeks of the baseline visit, participants will begin 5 daily sessions of TMS. The active group will have stimulation delivered to the brain via a coil. In the sham group, a dummy coil will be used that will not deliver stimulation. A total of three 3-minute cycles will be done in one visit. There will be 20-minute breaks between the cycles. Participants will have visits 1 month, 2 months, and 6 months after their last day of TMS. Their FMD symptoms will be evaluated. They will complete health questionnaires. These visits can be in person or virtual.
Detailed description
Study Description: The purpose of this protocol is to investigate efficacy of intermittent theta burst stimulation (iTBS) targeting the left dorsolateral prefrontal cortex (DLPFC) in patients with functional movement disorders (FMD). Participants will be randomly assigned to receive either active iTBS or sham stimulation of the left DLPFC for 5 consecutive daily sessions. Objectives: Primary Objective: To investigate efficacy of iTBS of the left DLPFC on motor symptoms in patients with FMD Secondary Objectives: To investigate efficacy of iTBS of the left DLPFC on mood symptoms and its effect on fronto-amygdala circuit on functional neuroimaging Endpoints: Primary Endpoint: Relative change in Functional Movement Disorder Rating Scale (S-FMDRS) from the baseline to 1 month after iTBS vs sham: 100 \*( S-FMDRS at one-month - S-FMDRS at baseline)/ S-FMDRS at baseline Secondary Endpoints: * S-FMDRS immediately after, 2 months and 6 months after the treatment * HADS at 1 month, 2 months and 6 months after the treatment * DLPFC-amygdala functional connectivity * Amygdala BOLD response to emotional stimuli
Interventions
DEVICEMagStim
Bursts of three at 50Hz with an inter burst interval of 200 ms will be given for 190 seconds and this session will be repeated 3 times with 20 minutes between each session in one day. The set of 3 sessions will be repeated 5 times in 5 consecutive days.
OTHERSham Comparator
Sham TMS stimulation using a sham coil
Sponsors
National Institutes of Health Clinical Center (CC)
National Institute of Neurological Disorders and Stroke (NINDS)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* INCLUSION CRITERIA: In order to be eligible to participate in this study, an individual must meet all of the following criteria: * Stated willingness to comply with all study procedures and availability for the duration of the study * Male or female, aged 18-80 * Diagnosis of functional movement disorder made by a neurologist * Agreement to adhere to Lifestyle Considerations throughout study duration * Ability of subject to understand and the willingness to sign a written informed consent document.
Exclusion criteria
An individual who meets any of the following criteria will be excluded from participation in this study: * Current psychosis or active suicidal ideation * History of epilepsy with the exception of febrile seizure * Patients with psychogenic non-epileptic seizure without comcomitant functional movement disorder * Any significant neurological disorders other than FMD including but not limited to multiple sclerosis, stroke, Parkinson s disease, space occupying brain lesion * Alcohol or substance use disorder * Patients who are on Buproprion (Wellbutrin) * Patients with moderate to severe cardiac disease * Any psychiatric, medical or social condition due to which, in the judgment of the PI and after any consults if indicated, participation in the study is not in the best interest of the patient. * Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in S-FMDRS at 1 Month After Real iTBS vs Sham iTBS | 1 month after iTBS | The Simplified Functional Movement Disorders Rating Scale (S-FMDRS) measures abnormal movements in 7 body regions as well as gait and speech. Symptom severity in each body region is rated from 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe) and duration from 0 to 3 (0=none; 1=occasionally, 2=frequent, 3= constant). All severity and duration scores are added to yield a total score. The total score ranges from minimum 0 to maximum 68, high score representing worse outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hospital Anxiety and Depression Scale (HADS) at 1, 2 and 6 Months After Real iTBS vs Sham iTBS | At baseline and 1, 2 and 6 months after iTBS | Hospital Anxiety and Depression Scale (HADS) is a continuous numeric scale in depression and anxiety (depression 0-21 and anxiety 0-21, higher score representing worse outcome) and the questions ask about the feeling in the past week. This was repeatedly measured at baseline, then at 1 month, 2 months and 6 months after iTBS vs sham and was compared between iTBS vs sham group. |
| CGI at 1, 2, and 6 Months After Real iTBS vs Sham iTBS | 1, 2 and 6 months after iTBS | The Clinical Global Impression (CGI) can assess patient's view of the patient's global functioning prior to and after initiating a study medication. The CGI scale of 1-7 is a measure of clinical improvement from the intervention, higher score presenting worse outcome. (1 = Very much improved, 2 = Much improved, 3 = Minimally improved, 4 = No change, 5 = Minimally worse, 6 = Much worse, 7 = Very much worse) |
| Change in S-FMDRS at 2 and 6 Months After Real iTBS vs Sham iTBS | 2 and 6 months after iTBS | The Simplified Functional Movement Disorders Rating Scale (S-FMDRS) measures abnormal movements in 7 body regions as well as gait and speech. Symptom severity in each body region is rated from 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe) and duration from 0 to 3 (0=none; 1=occasionally, 2=frequent, 3= constant). All severity and duration scores are added to yield a total score. The total score ranges from minimum 0 to maximum 68, high score representing worse outcome. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORDebra J Ehrlich, M.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Participant flow
Recruitment details
Study participants were recruited between May 2022 and March 2025 at National Institutes of Health Clinical Center located in Bethesda Maryland.
Pre-assignment details
Twenty-five participants consented to participate; one failed screening, and one was withdrawn prior to randomization due to newly identified exclusionary finding.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 22 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 17 Participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 2 Participants |
| S-FMDRS | 15.91 scores on a scale STANDARD_DEVIATION 8.75 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 12 |
| other Total, other adverse events | 8 / 11 | 3 / 12 |
| serious Total, serious adverse events | 0 / 11 | 0 / 12 |
Outcome results
None listed