Trial Outcomes & Findings for Neuroimaging Biomarkers of Prognosis in Motor Functional Neurological Disorders (NCT NCT03398070)

NCT ID: NCT03398070

Last Updated: 2023-08-29

Results Overview

Correcting for multiple comparisons in structural analyses, baseline structural grey matter volumes in limbic/paralimbic regions (particularly those affiliated with the salience network), would relate to clinical outcome in individuals receiving the standard of care at 6 months. Analyses reported refer to change in either mental health or physical health scores and baseline gray matter volume. The number presented is the peak voxel z-score as also reported in Supplementary Table 4 of the published manuscript. Z-scores are presented in absolute values (with the lowest value being 0). A higher z-score represents a stronger correlation between a given gray matter volume value (at the peak voxel) and the measure of interest (in case mental health or physical health scores). The entry under "row title" specifies if the association is a "positive" vs a "negative" association.

• Recruitment status: COMPLETED
• Target enrollment: 30 participants
• Primary outcome timeframe: baseline and 6 months
• Results posted on: 2023-08-29

Participant Flow

Participant milestones

Measure	Motor Functional Neurological Disorder. The cohort will consist of patients with clinically established motor functional neurological disorder, which includes individuals with functional movement disorders, psychogenic nonepileptic seizures and functional limb weakness. Patients will be receiving the standard of care within the Massachusetts General Hospital (MGH) Functional Neurological Disorders Clinic. The updated standard of care that patient's receive in the MGH Functional Neurological Disorders Clinic includes the following: 1. Delivery of a positive "rule-in" diagnosis of functional neurological disorder 2. Individuals are provided with educational materials on functional neurological disorders 3. Referred to physical therapy and/or occupational therapy as clinically indicated 4. FND related cognitive behavioral therapy (CBT) referral when appropriate 5. Psychotropic medication management based on standard psychiatric care Standard of Care: The standard of care interventions for Functional Neurological Disorders (FND) include: 1. delivery of a rule-in diagnosis 2. providing educational materials 3. referring to physical therapy (PT) and/or occupational therapy (OT) as clinically indicated 4. referring to FND-related cognitive behavioral therapy (CBT) 5. psychotropic medication management based on standard psychiatric care
Overall Study STARTED	30
Overall Study COMPLETED	22
Overall Study NOT COMPLETED	8

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Neuroimaging Biomarkers of Prognosis in Motor Functional Neurological Disorders

Baseline characteristics by cohort

Measure	Motor Functional Neurological Disorder. n=22 Participants The cohort will consist of patients with clinically established motor functional neurological disorder, which includes individuals with functional movement disorders, psychogenic nonepileptic seizures and functional limb weakness. Patients will be receiving the standard of care within the Massachusetts General Hospital (MGH) Functional Neurological Disorders Clinic. The updated standard of care that patient's receive in the MGH Functional Neurological Disorders Clinic includes the following: 1. Delivery of a positive "rule-in" diagnosis of functional neurological disorder 2. Individuals are provided with educational materials on functional neurological disorders 3. Referred to physical therapy and/or occupational therapy as clinically indicated 4. FND related cognitive behavioral therapy (CBT) referral when appropriate 5. Psychotropic medication management based on standard psychiatric care Standard of Care: The standard of care interventions for Functional Neurological Disorders (FND) include: 1. delivery of a rule-in diagnosis 2. providing educational materials 3. referring to physical therapy (PT) and/or occupational therapy (OT) as clinically indicated 4. referring to FND-related cognitive behavioral therapy (CBT) 5. psychotropic medication management based on standard psychiatric care
Age, Continuous	41.7 years STANDARD_DEVIATION 11.0 • n=5 Participants
Sex: Female, Male Female	19 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	22 Participants n=5 Participants
Region of Enrollment United States	22 Participants n=5 Participants

PRIMARY outcome

Timeframe: baseline and 6 months

Population: For this study, of an initially enrolled 30 participants, 22 provided followup data.

Correcting for multiple comparisons in structural analyses, baseline structural grey matter volumes in limbic/paralimbic regions (particularly those affiliated with the salience network), would relate to clinical outcome in individuals receiving the standard of care at 6 months. Analyses reported refer to change in either mental health or physical health scores and baseline gray matter volume. The number presented is the peak voxel z-score as also reported in Supplementary Table 4 of the published manuscript.

Z-scores are presented in absolute values (with the lowest value being 0). A higher z-score represents a stronger correlation between a given gray matter volume value (at the peak voxel) and the measure of interest (in case mental health or physical health scores). The entry under "row title" specifies if the association is a "positive" vs a "negative" association.

Outcome measures

Measure	Motor Functional Neurological Disorder. n=22 Participants The cohort will consist of patients with clinically established motor functional neurological disorder, which includes individuals with functional movement disorders, psychogenic nonepileptic seizures and functional limb weakness. Patients will be receiving the standard of care within the Massachusetts General Hospital (MGH) Functional Neurological Disorders Clinic. The updated standard of care that patient's receive in the MGH Functional Neurological Disorders Clinic includes the following: 1. Delivery of a positive "rule-in" diagnosis of functional neurological disorder 2. Individuals are provided with educational materials on functional neurological disorders 3. Referred to physical therapy and/or occupational therapy as clinically indicated 4. FND related cognitive behavioral therapy (CBT) referral when appropriate 5. Psychotropic medication management based on standard psychiatric care Standard of Care: The standard of care interventions for Functional Neurological Disorders (FND) include: 1. delivery of a rule-in diagnosis 2. providing educational materials 3. referring to physical therapy (PT) and/or occupational therapy (OT) as clinically indicated 4. referring to FND-related cognitive behavioral therapy (CBT) 5. psychotropic medication management based on standard psychiatric care
Gray Matter Volume Biomarkers of 6 Month Prognosis as Measured by Voxel Based Morphometry - Within Group Comparison ∆SF-36 Mental Health Positive Associations: L anterior hippocampus: -34mm, -16mm, -15mm	3.76 peak voxel z-score
Gray Matter Volume Biomarkers of 6 Month Prognosis as Measured by Voxel Based Morphometry - Within Group Comparison ∆SF-36 Mental Health Positive Associations: L middle frontal gyrus (46): -33mm, 26mm, 40mm	3.61 peak voxel z-score
Gray Matter Volume Biomarkers of 6 Month Prognosis as Measured by Voxel Based Morphometry - Within Group Comparison ∆SF-36 Mental Health Positive Associations: R supplementary motor area (6): 10mm, -16mm, 75mm	4.18 peak voxel z-score
Gray Matter Volume Biomarkers of 6 Month Prognosis as Measured by Voxel Based Morphometry - Within Group Comparison ∆SF-36 Mental Health Positive Associations: R superior frontal gyrus (6): 18mm, -7mm, 72mm	3.27 peak voxel z-score
Gray Matter Volume Biomarkers of 6 Month Prognosis as Measured by Voxel Based Morphometry - Within Group Comparison ∆SF-36 Physical Health Positive Associations: R frontopolar cortex (10): 10mm, 62mm, 4mm	3.90 peak voxel z-score
Gray Matter Volume Biomarkers of 6 Month Prognosis as Measured by Voxel Based Morphometry - Within Group Comparison ∆SF-36 Physical Health Negative Associations: R superior/middle frontal gyrus (9): 22mm, 24mm, 37mm	4.40 peak voxel z-score
Gray Matter Volume Biomarkers of 6 Month Prognosis as Measured by Voxel Based Morphometry - Within Group Comparison ∆SF-36 Physical Health Negative Associations: L superior occipital gyrus (19): -10mm, -82mm, 45mm	3.80 peak voxel z-score
Gray Matter Volume Biomarkers of 6 Month Prognosis as Measured by Voxel Based Morphometry - Within Group Comparison ∆SF-36 Physical Health Negative Associations: L superior occipital gyrus (19): -18mm, -78mm, 42mm	3.70 peak voxel z-score
Gray Matter Volume Biomarkers of 6 Month Prognosis as Measured by Voxel Based Morphometry - Within Group Comparison ∆SF-36 Mental Health Positive Associations: R middle cingulate gyrus (24): 3mm, 12mm, 43mm	3.85 peak voxel z-score

PRIMARY outcome

Timeframe: baseline and 6 months

Population: For this study, of an initially enrolled 30 participants, 22 provided followup data.

Correcting for multiple comparisons in resting state connectivity analyses, baseline functional connectivity strength (t-statistic scores) across limbic/paralimbic regions (particularly those affiliated with the salience network), would relate to clinical outcome in individuals receiving the standard of care at 6 months. Here, we tested if link-step connectivity from primary motor areas or amygdala nuclei related to change in clinical outcome. Specifically, we are providing the t-statistic for the connectivity strength between left centromedial amygdala to right anterior insula.

Functional connectivity strength is based on the correlation of low frequency brain oscillations measured at rest. A large t-statistic value reflects greater connectivity between brain voxels.

Outcome measures

Measure

Motor Functional Neurological Disorder. n=22 Participants The cohort will consist of patients with clinically established motor functional neurological disorder, which includes individuals with functional movement disorders, psychogenic nonepileptic seizures and functional limb weakness. Patients will be receiving the standard of care within the Massachusetts General Hospital (MGH) Functional Neurological Disorders Clinic. The updated standard of care that patient's receive in the MGH Functional Neurological Disorders Clinic includes the following: 1. Delivery of a positive "rule-in" diagnosis of functional neurological disorder 2. Individuals are provided with educational materials on functional neurological disorders 3. Referred to physical therapy and/or occupational therapy as clinically indicated 4. FND related cognitive behavioral therapy (CBT) referral when appropriate 5. Psychotropic medication management based on standard psychiatric care Standard of Care: The standard of care interventions for Functional Neurological Disorders (FND) include: 1. delivery of a rule-in diagnosis 2. providing educational materials 3. referring to physical therapy (PT) and/or occupational therapy (OT) as clinically indicated 4. referring to FND-related cognitive behavioral therapy (CBT) 5. psychotropic medication management based on standard psychiatric care

Resting State Functional Connectivity Strength Biomarkers of 6 Month Prognosis - Within Group Comparison

4.58 t-statistic

PRIMARY outcome

Timeframe: baseline and 6 months

Population: we focused on our T1-weighted structural and functional connectivity analyses during this K23 grant period.

Baseline integrity of the cingulum bundle and cingulate-insular tracts, as measured by fractional anisotropy, would relate to 6 month prognosis in patients with Functional Neurological Disorders (FND) receiving the standard of care.

Outcome was not assessed - no time to analyze data given prior challenges with the pandemic. Unable to report data in any table as the white matter images have not been analyzed.

Outcome measures

Outcome data not reported

Adverse Events

Motor Functional Neurological Disorder.

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

David Perez

Massachusetts General Hospital

Phone: 6177262000

Email: dlperez@partners.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place