Definition of Autonomic Nervous System Involvement in Patients With Multiple Sclerosis

Study Overview
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Brief Summary
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The goal of this interventional non-pharmacological study is to evaluate the involvement of the autonomic nervous system in patients with relapsing-remitting and primary progressive multiple sclerosis. The main questions it aims to answer are: Is it possible to define the characteristics of dysautonomia to improve treatment on patients with multiple sclerosis through the management of conditions such as orthostatic hypotension or thermoregulation disorders that inevitably condition the patient's life and the response to rehabilitation ? Does the severity of the functional alterations correlate with impairment of small somatic and autonomic cutaneous nerve fibers in patients with multiple sclerosis ? How much the involvement of the autonomic nervous system affects the clinical history and progression of the disease ? Do different clinical variants of multiple sclerosis manifest with different patterns of involvement of the sensory-autonomic nervous system ? Participants will be hospitalized in Maugeri Clinical Institute of Telese Terme for a rehabilitation treatment. Patients will perform a sensory and autonomic functional study and a morphological analysis of cutaneous nerves through skin biopsy. Researchers will compare results between the two groups (relapsing-remitting and primary progressive) and between patients and data from control subjects.

Official Title
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Definition of Autonomic Nervous System Involvement in Patients With Relapsing-remitting and Primary Progressive Multiple Sclerosis

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Diagnostic Test: quantification of sensory and autonomic small nerve fibers by punch skin biopsy
* Diagnostic Test: Cardiovascular Reflexes testing
* Other: Administration of clinical scales evaluating autonomic symptoms, pain small fiber neuropathy symptoms


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diagnosis of relapsing-remitting and primary progressive multiple sclerosis. Exclusion Criteria: other forms of multiple sclerosis, known other neurological disorders assumption of potentially neurotoxic substances or drugs.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: relapsing-remitting multiple sclerosis<br>Patients with relapsing-remitting multiple sclerosis will be hospitalized in Maugeri Clinical Institute of Telese Terme for a rehabilitation treatment and will perform a functional and morphological study of sensory and autonomic nervous system, evaluation of peripheral sensory and autonomic nerve fibers performed by skin biopsy. | Diagnostic Test: quantification of sensory and autonomic small nerve fibers by punch skin biopsy<br>* We'll perform a punch skin biopsy of 3mm from thigh, leg and fingertip and we'll quantify peripheral sensory and autonomic nerve fibers.<br>Diagnostic Test: Cardiovascular Reflexes testing<br>* Cardiovascular reflex tests including deep breathing, head-up Tilt, standing, isometric exercises, mental arithmetic and Valsalva maneuver.<br>Other: Administration of clinical scales evaluating autonomic symptoms, pain small fiber neuropathy symptoms<br>* We'll characterize patients' symptoms through the administration of clinical scales such as: COMPASS 31 autonomic symptoms scale; Small Fiber Neuropathy Symptom Inventory Questionnaire (SFN-SIQ), the Pain Detect Questionnaire and the Total neuropathy score<br>|
| Active Comparator: primary progressive multiple sclerosis<br>Patients with primary progressive multiple sclerosis will be hospitalized in Maugeri Clinical Institute of Telese Terme for a rehabilitation treatment and will perform a functional and morphological study of sensory and autonomic nervous system, evaluation of peripheral sensory and autonomic nerve fibers performed by skin biopsy. | Diagnostic Test: quantification of sensory and autonomic small nerve fibers by punch skin biopsy<br>* We'll perform a punch skin biopsy of 3mm from thigh, leg and fingertip and we'll quantify peripheral sensory and autonomic nerve fibers.<br>Diagnostic Test: Cardiovascular Reflexes testing<br>* Cardiovascular reflex tests including deep breathing, head-up Tilt, standing, isometric exercises, mental arithmetic and Valsalva maneuver.<br>Other: Administration of clinical scales evaluating autonomic symptoms, pain small fiber neuropathy symptoms<br>* We'll characterize patients' symptoms through the administration of clinical scales such as: COMPASS 31 autonomic symptoms scale; Small Fiber Neuropathy Symptom Inventory Questionnaire (SFN-SIQ), the Pain Detect Questionnaire and the Total neuropathy score<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiovascular reflex test | Assessment of Cardiovascular reflex responses to physical challenges. | At the recruitment | 
| Sudomotor function test | Assessment of postganglionic sudomotor function through dynamic sweat test | At the recruitment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantification of peripheral autonomic nerve fibers | Quantification of sweat gland innervation (fiber length /um3) and arrector pili muscle (ff/mm). | At the recruitment | 
| Quantification of peripheral sensory nerve fibers | Quantification of sensory nerve fibers (Intraepidermal nerve fibers (ff/mm)). | At the recruitment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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autonomic nervous system, sensory nervous system, rehabilitation, skin biopsy