Integrated Treatment in FND (Functional Neurological Disorders)

Study Overview
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Brief Summary
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The project will investigate the effectiveness of patient-centered integrated treatment. The correlations between physiotherapy indices, non-invasive brain stimulation, connectivity and psychological support will be analyzed.

Detailed Description
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At the time of recruitment (T0) a multidimensional evaluation will be performed consisting of clinical, neuropsychological, neurophysiological, MRI, data obtained from peripheral blood sampling (10ml). After completing the program (12 weeks), the effect will be assessed according to objectives (T1). The study will also include a follow-up evaluation after 6 months (T2) and 12 months (T3) from the beginning of the treatment to evaluate the persistence of the beneficial effects after some time.

Official Title
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Role of Integrated Treatment in Patients With Functional Neurological Disorder

Conditions
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Functional Neurological Disorder

Intervention / Treatment
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* Other: Psychotherapy
* Behavioral: Physiotherapy
* Other: Non-Invasive Brain Stimulation (NIBS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to provide written informed consent Diagnosis of Functional Neurological Disorder of movement clinically established according to DSM-5 criteria Age between 18 and 65 years (inclusive) Ability to participate in the study protocol Exclusion Criteria: Inability to provide written informed consent Pregnant women In case of use of non-invasive brain stimulation techniques: the subjects must not present any of the contraindications specific to this method (for further specifications see the Methods and the Stimulation Evaluation Questionnaire attached to this proposal) Presence of unstable clinical conditions or infections In the case of the use of non-invasive brain stimulation techniques: concomitant use of drugs that can alter the transmission and synaptic plasticity (cannabinoids, L-dopa, antiepileptics, nicotine, baclofen, Selective Serotonin Reuptake Inhibitors (SSRI), botulinum toxin) Inability to support physiotherapy or psychotherapy sessions

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients with FND<br>Diagnosis of Functional Neurological Disorder of movement clinically established according to Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria | Other: Psychotherapy<br>* The patient will be treated according to Lacanian psychoanalytic ethics, which allows to adequately respond to the patient's request for healing but who at the same time does not ignore the progress of scientific research in the neurological field<br>Behavioral: Physiotherapy<br>* Physiotherapy treatment will be articulated through the use of techniques designed to qualify the functionality of the subject divided by symptom: weakness, dystonic attitudes of the limbs, walking disorders, tremor.<br>Other: Non-Invasive Brain Stimulation (NIBS)<br>* Diversified transcranial electrical maneuver protocols with an on-line or off-line approach may be applied for therapeutic purposes. This will include: transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), random noise stimulation (tRNS).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes and improvement in clinical condition | the Clinical global impression scale will be used. It is a brief 3-item observer-rated scale that assess severity of illness with assignable scores ranging from 0 to 7 (at every time time point), the global improvement with assignable scores ranging from 0 to 7 (from the second time point), and the efficacy index with assignable scores ranging from 1 to 16 (relationship between therapeutic efficacy and undesirable effects). Higher scores on these scales mean a worse outcome. | 1-12 months | 
| Changes in quality of life | The Short Form Health Survey 36 (SF-36) will be used. It is a generic, multidimensional tool, consisting of 36 questions that can be divided into 8 scales (Physical functioning, limitations due to physical health, limitations due to emotional problems, energy and fatigue, emotional well-being, social activities, pain, general health perception) expressed as percentage values 0-100%. Higher scores on these scales mean a better quality of life. | 1-12 months | 
| Changes in executive functions and attention - step 1 | Will be used the Symbol Digit Modalities Test, which measures the processing speed, in the oral version of this test (Nocentini et al., 2006). The assignable performance's scores ranging from 0 to 110. The cut-off for normality in italian population for this oral version was 34.2. Higher scores on these scales mean a better processing speed. | 1-12 months | 
| Changes in executive functions and attention - step 2 | Stroop test | 1-12 months | 
| Changes in neuroplasticity | Transcranial Magnetic Stimulation (TMS) will be used to evaluate the change of neuronal plasticity in a subgroup of patients who will not present contraindications to the method. The TMS uses short-lived magnetic fields and high intensity applied at the scalp level to activate the neurons of a small region of the cerebral cortex through an electromagnetic induction. When these impulses are applied repeatedly, it is possible to induce plastic modification of cortical excitability. Any increase or decrease in amplitude, which persists after the end of TMS repetitive stimulation, indicates that there have been changes in the cortical, long term potentiation (LTP) or depression (LTD). | 1-12 months | 
| Evaluation of genetic polymorphisms | A blood sample (10 ml) will be collected to investigate whether genetic polymorphisms related to patients' neuronal plasticity can be related to the response to the protocol. | 1-12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in behavioral aspects - step 1 | State-Trait Anxiety Inventory-Form Y (STAI-Y). The STAI-Y is a self-report questionnaire consisting of two 20-item scales providing separate measures of state and trait anxiety, on a 4-point Likert scale, with scores ranges from 20 to 80, with higher scores indicating more severe outcome. | 1-12 months | 
| Changes in behavioral aspects - step 2 | Beck Depression Inventory - Second Edition (BDI-II). BDI-II is a self-report questionnaire consisting of 21-item self-report scale designed to measure the severity of depressive symptoms, on a 4-point Likert scale, with scores ranges from 0 to 63, with higher scores indicating more severe outcome. | 1-12 months | 
| Changes in behavioral aspects - step 3 | Toronto Alexithymia Scale (TAS-20). TAS-20 is a self-report questionnaire scale designed to measure alexithymia, on a 5-point Likert scale, with scores ranges from 20 to 100, with higher scores indicating more severe outcome. | 1-12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FND, physiotherapy, psychotherapy, non-invasive brain stimulation