Neuroimaging Biomarkers of Prognosis in Motor Functional Neurological Disorders

NCT03398070 | Completed Results

• 1 other identifier: 1K23MH111983-01A1
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Functional Neurological Disorder (FND/ Conversion Disorder) is a highly prevalent and disabling neuropsychiatric condition. Motor FND symptoms include Nonepileptic Seizures, Functional Movement Disorders and Functional Weakness. Clinical research across these motor FND subtypes, including research studies from the candidate's laboratory, suggest that these populations share many clinical and phenotypic similarities that warrant increased research integration. Furthermore, despite the prevalence of motor FND, little is known about the underlying pathophysiology of this condition, which is a prerequisite for the development of biologically informed prognostic and treatment response biomarkers. Across 3 published neurobiologically focused articles, the candidate proposed a framework through which to conceptualize motor FND. It is suggested that motor FND develops in the context of structural and functional alterations in neurocircuits mediating emotion awareness/expression, bodily awareness, viscerosomatic processing and behavioral regulation. The overall goal of this project is to comprehensively investigate structural and functional magnetic resonance imaging (MRI) biomarkers of prognosis across motor FND. Multimodal structural and functional MRI techniques (including voxel-based morphometry, cortical thickness, resting-state functional connectivity and diffusion tensor imaging tractography) will be used to systemically probe brain-prognosis relationships. Novel aspects of this proposal include the study of the full spectrum of motor FND, consistent with a trans-diagnostic approach.

Conditions

Conversion Disorder

Keywords

Functional Neurological Disorder; Functional Movement Disorder; Psychogenic Nonepileptic Seizures; Functional Limb Weakness

Outcome Measures

Primary Outcomes (3)

• Gray Matter Volume Biomarkers of 6 Month Prognosis as Measured by Voxel Based Morphometry - Within Group Comparison

  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.

  baseline and 6 months

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

  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.

  baseline and 6 months

• The Integrity of Specific White Matter Tracts (Fractional Anisotropy) as Measured by Diffusion Tensor Imaging (DTI) Tractography Will Relate to 6-month Prognosis

  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.

  baseline and 6 months

Study Arms (1)

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

Other: Standard of Care

Interventions

Standard of Care OTHER

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

Motor Functional Neurological Disorder.

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Recruitment will occur from patients receiving care in the Massachusetts General Hospital (MGH) Functional Neurological Disorders Clinic

You may qualify if:

• clinically established motor functional neurological disorder, including individuals with functional movement disorders, functional limb weakness and psychogenic nonepileptic seizures

You may not qualify if:

• active suicidality
• major medical/neurological comorbidities with known central nervous system (CNS) consequences
• active drug use or alcohol dependence
• known history of a primary psychotic disorder

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (2)

• Diez I, Ortiz-Teran L, Williams B, Jalilianhasanpour R, Ospina JP, Dickerson BC, Keshavan MS, LaFrance WC Jr, Sepulcre J, Perez DL. Corticolimbic fast-tracking: enhanced multimodal integration in functional neurological disorder. J Neurol Neurosurg Psychiatry. 2019 Aug;90(8):929-938. doi: 10.1136/jnnp-2018-319657. Epub 2019 Mar 8.

  PMID: 30850473 RESULT

• Perez DL, Williams B, Matin N, Mello J, Dickerson BC, LaFrance WC Jr, Keshavan MS. Anterior hippocampal grey matter predicts mental health outcome in functional neurological disorders: an exploratory pilot study. J Neurol Neurosurg Psychiatry. 2018 Nov;89(11):1221-1224. doi: 10.1136/jnnp-2017-317305. Epub 2018 Jan 11. No abstract available.

  PMID: 29326291 RESULT

Related Links

• See Figure 5 for relevant results
• See Figure 1 for relevant results

MeSH Terms

Conditions

Conversion Disorder; Psychogenic Nonepileptic Seizures

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Somatoform Disorders; Mental Disorders; Seizures; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Limitations and Caveats

Limitations include a modest sample size, patient heterogeneity, medication use, reliance on self-report measures and that management was not restricted to one institution.

Results Point of Contact

• Title: David Perez
• Organization: Massachusetts General Hospital

dlperez@partners.org

6177262000

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 15, 2017
• First Posted: January 12, 2018
• Study Start: September 1, 2017
• Primary Completion: January 20, 2023
• Study Completion: January 20, 2023
• Last Updated: August 29, 2023
• Results First Posted: August 29, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)