A Window Into the Mind-brain-body Interplay: Development of Diagnostic, Prognostic Biomarkers and Rehabilitation Strategies in Functional Motor Disorders
Trial ID: NCT06328790
Status: UNKNOWN
Study type: OBSERVATIONAL
Start date: 2023-05-31
Completion date: 2025-05
Sponsor: Michele Tinazzi, MD, PhD
Collaborators: IRCCS Ospedale San Raffaele; Azienda Ospedaliera OO.RR. S. Giovanni di Dio e Ruggi D'Aragona
Conditions: Functional Motor Disorders
Interventions: Multidisciplinary Rehabilitation Training; Cross-sectional study on patients with FMD and patients with structural/organic diseases; Cross-sectional study on patients with FMD and healthy controls (HC)
Locations: Azienda Ospedaliera OO.RR. S. Giovanni di Dio e Ruggi D'Aragona; IRCCS Ospedale San Raffaele; Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona
Countries: Italy; Italy; Italy
Enrollment: 450
Age range: 18 Years - None
Sex: ALL

Summary:
Functional motor disorders (FMD) are prevalent and highly disabling conditions characterized by abnormal movements (functional weakness, tremor, dystonia) significantly altered by distractive manoeuvres and incongruent with movement disorders seen in specific neurological diseases. FMDs are still misunderstood, diagnosed with delay, and not adequately treated, leading to reduced independence and high healthcare costs. Symptoms are physiologically associated with voluntary movement (distractibility, resolution with placebo) but are reported as involuntary. How this happens is yet a matter of debate. Identifying diagnostic and prognostic disease-specific biomarkers is an unmet need. The investigators will investigate motor, exteroceptive and interoceptive domains in a large cohort of FMD patients by a comprehensive set of behavioural, neurophysiological, and MRI tests. Ad-hoc eXplainable Artificial Intelligence (XAI) methods will develop disease-specific diagnostic and prognostic biomarker algorithms.

Eligibility criteria:
Experiments 1 and 3

Inclusion Criteria for Patients with FMD:

* Age higher or equal to 18 years
* Clinically definite diagnosis of FMD

Exclusion Criteria for Patients with FMD:

* Mini-Mental State Examination score lower or equal to 24
* Physical impairment precluding signing the informed consent for participation
* Certified other neurological and/or psychiatric comorbidities
* Contraindications for 3T MRI

Inclusion Criteria for Healthy Controls (HC)

\- Age higher or equal to 18 years

Exclusion Criteria for Healthy Controls (HC) Mini-Mental State Examination score lower or equal to 24

* Physical impairment precluding signing the informed consent for participation
* Certified neurological and/or psychiatric comorbidities
* Contraindications for 3T MRI

Experiment 2

Inclusion criteria

* Age higher or equal to 18 years
* Clinically definite diagnosis of "organic" motor disorders: weakness due to peripheral neuromuscular disorders, essential tremor, or idiopathic adult-onset dystonia.
* Score\>2 on the Tremor Research Group Essential Tremor Rating Assessment Scale for patients with essential tremor
* Rest tremors and other neurological signs
* Current or past exposure to tremorgenic drugs

Exclusion Criteria

* Mini-Mental State Examination score lower or equal to 24
* Physical impairment precluding signing the informed consent for participation
* Certified neurological and/or psychiatric comorbidities
* Contraindications for 3T MRI

Outcomes:
Simplified Functional Movement Disorders Rating Scale (S-FMDRS) score; Multidimensional Fatigue Inventory Scale (MFI-20) score; Brief Pain Inventory (BPI) score; Beck Anxiety Inventory (BAI) score; Beck Depression Inventory (BDI-II) score; 12-item Short-Form Health Survey (SF-12) score; Toronto Alexithymia Scale (TAS-20) score; Direct adn indirect index of Sensory Attenuation (SA); Joint angle at the elbow vibrated and reproduced; N2/P2 amplitude; Objective/Subjective heart rate ratio; Cortical thickness and gray matter volumes; Clinical Global Impression (CGI) score; Gait speed (cm/sec); Swing time (%); Stride time (s); Stride length (cm); Sway area (mm2); Stance time (sec); Total excursion path (mm); Velocity of Cop displacement in the anteroposterior directions (mm/s); Velocity of Cop displacement in the mediolateral directions (mm/s); Autism spectrum Quotient (AQ); Schizotypal Personality Questionnaire (SPQ)