Neuroimaging Biomarkers of Prognosis in Motor Functional Neurological Disorders

NCT ID: NCT03398070

Last Updated: 2023-08-29

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

30 participants

Study Classification

OBSERVATIONAL

Study Start Date

2017-09-01

Study Completion Date

2023-01-20

Brief Summary

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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.

Detailed Description

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Functional Neurological Disorder (FND) (Conversion Disorder) is a poorly understood and prevalent somatoform disorder, making up 16% of outpatient neurology referrals. Patients with motor FND (mFND) are difficult to treat, result in major morbidity, and are costly to the US. An estimated $256 billion is spent annually treating this population. mFND includes Nonepileptic Seizures (NES), Functional Movement Disorders (FMD) and Functional Weakness (FW). An impediment to managing mFND is the lack of a neurobiological understanding for this disorder. The diagnosis of mFND is currently based on qualitative aspects of behaviors, which may be difficult to interpret, and the absence of findings characteristic of other neuropsychiatric disorders on laboratory studies such as electroencephalography (EEG) and magnetic resonance imaging (MRI).

A major step forward would be the identification of neuroimaging biomarkers for mFND. mFND is understudied compared to other disorders, but recent studies point to distributed neurocircuit alterations associated with mFND. This project aims to advance our biological understanding of mFND by investigating neuroimaging biomarkers linked to prognosis. An improved understanding of the pathophysiology of mFND will provide a critical step in elucidating diagnostic, prognostic and treatment response biomarkers.

Aim:

Identify structural and functional biomarkers of prognosis at 6-months in patients with motor functional neurological disorders receiving an updated standard of care.

H1: Favorable mFND prognosis at 6 months post initial evaluation will be predicted by the degree of preserved baseline gray matter in limbic-paralimbic regions, particularly those part of the salience network.

H2: Favorable mFND prognosis at 6 months post initial evaluation will be predicted by the degree of preserved baseline resting-state functional connectivity in limbic/paralimbic areas, particularly those part of the salience network.

H3: Favorable mFND prognosis at 6 months will correlate with the degree of preserved baseline cingulum bundle and cingulum-insular tract integrity.

Conditions

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Conversion Disorder

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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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

Intervention Type 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

Interventions

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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

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

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

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Massachusetts General Hospital

OTHER

Sponsor Role lead

Responsible Party

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David Lewis Perez

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Countries

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United States

References

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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.

Reference Type RESULT
PMID: 30850473 (View on PubMed)

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.

Reference Type RESULT
PMID: 29326291 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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https://jnnp.bmj.com/content/90/8/929.long

See Figure 5 for relevant results

https://jnnp.bmj.com/content/89/11/1221.long

See Figure 1 for relevant results

Other Identifiers

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1K23MH111983-01A1

Identifier Type: NIH

Identifier Source: org_study_id

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