Exploring Functional Paralysis With Advanced Magnetic Resonance Modalities

In functional neurological disorder (FND), neurological symptoms are present, such as paralysis, weakness and disturbed sensation of limbs, although clinically no abnormalities can be found. It is a poorly understood disorder with uncertain diagnosis, treatment and prognosis. In this study, the subtype functional paralysis is investigated with advanced neuroimaging techniques that go beyond standard clinical examinations. In previous research on FND, healthy volunteers have generally been used as a control group. However, since people with functional paralysis have similar symptoms to people with spinal cord injuries (SCI), it is intended to compare the three groups to find similarities and differences. With the proposed methods, the goal is to gain a detailed understanding of FND regarding nerve cell metabolism, diffusion pathways and neuronal networks involved in cognitive processes such as motor inhibition (reaction or no reaction depending on situation). Neurophysiological data, clinical assessments and questionnaires are carried out in addition to Magnetic Resonance Imaging (MRI).

The aim is to enrol 75 participants in this study, i.e. 25 people with FND, 25 people with SCI and 25 healthy control subjects.

The overall goal of the study is to find markers for FND for use in future studies to improve diagnosis and individualise therapy recommendation for both people with SCI and people with FND. Therefore, this study is a relevant step to understand FND and to diagnose this specific disease using objective MRI based diagnostic tools.

Study Overview

• Status: Completed
• Conditions: Paralysis; Functional Neurological Symptom Disorder; Conversion Disorder With Weakness/Paralysis
• Intervention / Treatment: Diagnostic test: Magnetic Resonance Imaging (MRI)

• Study Type: Observational
• Enrollment (Actual): 69

Contacts and Locations

• Study Contact: Name: Vanessa Vallesi, MSc; Phone Number: 0041419396012; Email: vanessa.vallesi@paraplegie.ch

Study Locations

• Switzerland
  • Lucerne
    • Nottwil, Lucerne, Switzerland, 6207
      • Swiss Paraplegic Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

FND patients are recruited at the Swiss Paraplegic Centre and the Inselspital Bern. Inpatient and outpatient SCI subjects are recruited in the Swiss Paraplegic Centre .

Description

Inclusion Criteria:

• Age between 18-65

Exclusion Criteria:

• Contraindication for magnetic resonance examinations (e.g. cardiac pacemaker, pregnancy, etc.)
• history of mental or neurological illness (addiction, central nervous system tumour and severe craniocerebral trauma)
• unable to hold a pen due to paralysis

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
control; Healthy participants	Diagnostic test: Magnetic Resonance Imaging (MRI); In order to investigate the metabolic profile, magnetic resonance spectroscopy (MRS) will be applied. Functional MRI (fMRI) allows to indirectly track cell activation measuring the blood-level dependent signal changes followed spontaneously (in resting state) or evoked by a task. Diffusion weighted imaging (DWI) is based on the differences in motion of the water molecules given by the underlying microarchitecture of the nervous tissue. Diffusion tensor imaging (DTI) allows visualisation of the nerve bundles and alterations thereof. Thus, microstructural alterations can be measured.; Other Names: Functional Magnetic Resonance Imaging (fMRI); In-vivo Magnetic Resonance Spectroscopy (MRS); Diffusion Tensor Imaging (DTI); Diffusion Weighted Imaging (DWI)
Functional Neurological Disorder (FND); People with the subtype functional paralysis	Diagnostic test: Magnetic Resonance Imaging (MRI); In order to investigate the metabolic profile, magnetic resonance spectroscopy (MRS) will be applied. Functional MRI (fMRI) allows to indirectly track cell activation measuring the blood-level dependent signal changes followed spontaneously (in resting state) or evoked by a task. Diffusion weighted imaging (DWI) is based on the differences in motion of the water molecules given by the underlying microarchitecture of the nervous tissue. Diffusion tensor imaging (DTI) allows visualisation of the nerve bundles and alterations thereof. Thus, microstructural alterations can be measured.; Other Names: Functional Magnetic Resonance Imaging (fMRI); In-vivo Magnetic Resonance Spectroscopy (MRS); Diffusion Tensor Imaging (DTI); Diffusion Weighted Imaging (DWI)
Spinal Cord Injury (SCI); Incomplete and complete paralysis with the ability to hold a pen	Diagnostic test: Magnetic Resonance Imaging (MRI); In order to investigate the metabolic profile, magnetic resonance spectroscopy (MRS) will be applied. Functional MRI (fMRI) allows to indirectly track cell activation measuring the blood-level dependent signal changes followed spontaneously (in resting state) or evoked by a task. Diffusion weighted imaging (DWI) is based on the differences in motion of the water molecules given by the underlying microarchitecture of the nervous tissue. Diffusion tensor imaging (DTI) allows visualisation of the nerve bundles and alterations thereof. Thus, microstructural alterations can be measured.; Other Names: Functional Magnetic Resonance Imaging (fMRI); In-vivo Magnetic Resonance Spectroscopy (MRS); Diffusion Tensor Imaging (DTI); Diffusion Weighted Imaging (DWI)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nerve Cell Metabolism	With MRS metabolites are examined specific for cell integrity (N-acetyl-aspartate), cell energy (creatine, lactate), and neurotransmitter (choline, glutamate and glutamine).	day 1
Brain Functional Connectivity	With fMRI in rest and task condition, the functional connectivity (FC) is examined. With that the functionally integrated relationship between spatially separated brain regions are investigated.	day 1
Fiber tracts in three dimensional mapping	DWI provides quantitative evaluations by measuring the apparent diffusion coefficient (ADC) and fractional anisotropy (FA), which are scalars of isotropic and anisotropic diffusion. Diffusion tensor imaging (DTI) analyses the three-dimensional shape of the diffusion, also known as diffusion tensor. So, it is used to characterize the magnitude, the degree of anisotropy, and the orientation of directional diffusion of white matter.	day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Satisfaction with Life Scale questionnaire	Likert Scale of 1 (strong disagreement) -7 (strong agreement); 5 Questions in total	day 1
Hospital Anxiety and Depression Scale questionnaire	Likert Scale of 1 (strong disagreement) -4 (strong agreement); 14 Questions in total	day 1
Numerical Rating Scale (NRS) questionnaire	Rating the pain on a likert scale of 0 (no pain) -10 (insupportable pain)	day 1
Sensibility testing according to International Standards for Neurological Classification of SCI (ISNCSCI)	A key point in each of the 28 dermatomes is tested bilaterally using light touch and pin-prick (sharp-dull discrimination). A three-point scale is used for scoring: 0 = absent; = altered (impaired or partial appreciation, including hyperesthesia); = normal or intact (similar as on the cheek) not testable	day 1

Collaborators and Investigators

• Sponsor: Swiss Paraplegic Research, Nottwil

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2022
• Primary Completion (Actual): February 8, 2024
• Study Completion (Actual): February 8, 2024

Study Registration Dates

• First Submitted: November 17, 2021
• First Submitted That Met QC Criteria: November 17, 2021
• First Posted (Actual): December 1, 2021

Study Record Updates

• Last Update Posted (Actual): March 8, 2024
• Last Update Submitted That Met QC Criteria: March 7, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Personality Disorders; Somatoform Disorders; Histrionic Personality Disorder; Paralysis; Dissociative Disorders; Conversion Disorder; Hysteria
• Other Study ID Numbers: 2021-10

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No