Clinical trial NCT04220814: Evaluation of the Impact of Lesions of the Motor and Proprioceptive Brain and Pan-medullary Pathways on Their Clinically and Electrophysiologically Assessed Function in Multiple Sclerosis
Official title: Evaluation of the Impact of Lesions of the Motor and Proprioceptive Brain and Pan-medullary Pathways on Their Clinically and Electrophysiologically Assessed Function in Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Multiple Sclerosis, Relapsing-Remitting
Keywords: Multiple sclerosis
MRI
pronostic
Lead sponsor: Rennes University Hospital
Sponsor class: OTHER
First posted: 2020-01-07
Enrollment: 94
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: Multiple Sclerosis (MS) is the most common acquired neurological disease leading to disability, especially ambulatory, in young adults. To date, the correlation between the number or volume of white matter lesions seen on conventional MRI and the degree of disability of patients remains low to moderate. This phenomenon is known as the "clinical-radiological paradox".

In this new project, we hypothesize that an evaluation of the corticospinal pathways including their thoracic medullary portion, as well as taking into account the severity of the lesions using quantitative MRI, will allow the investigators to refine the correlation with ambulatory disability in MS patients. We will complete the evaluation of motor pathways with those of the proprioceptive pathways also strongly involved in ambulation.

Detailed description: Multiple Sclerosis (MS) is the most common acquired neurological disease leading to disability, especially ambulatory, in young adults. To date, the correlation between the number or volume of white matter lesions seen on conventional MRI and the degree of disability of patients remains low to moderate. This phenomenon is known as the "clinical-radiological paradox".

The impact of the precise localisation of focal MS lesions on certain circuits particularly involved in ambulation, such as pyramidal or proprioceptive beams, has however been little studied in imaging, mainly due to technical limitations. Indeed, such studies require the acquisition of brain and spinal cord MRI images of sufficient spatial resolution to allow the localisation of focal lesions and pathways. Several previous studies have shown encouraging results by separately studying damage to the brain or spinal cord portion of the corticospinal bundle and relating it to disability. To our knowledge, no studies have analysed the lesional involvement of the cortico-spinal bundle or the entire proprioceptive bundle from the motor cortex to the medullary cone in patients with MS.

In a preliminary study, we studied the cerebral spinal cortex and cervical spinal cord bundle using data from the PHRC 2012 EMISEP and obtained encouraging results. In particular, we have shown that the cortico-spinal pathways are very frequently affected by focal lesions in the early years of the disease and that it is already correlated with the functional consequences in patients measured clinically and in electrophysiology.

In this new project, we hypothesize that an evaluation of the corticospinal pathways including their thoracic medullary portion, as well as taking into account the severity of the lesions using quantitative MRI, will allow the investigators to refine the correlation with ambulatory disability in MS patients. We will complete the evaluation of motor pathways with those of the proprioceptive pathways also strongly involved in ambulation.

Eligibility criteria: Inclusion Criteria:

Patients :

* More than 18 years old
* relapsing-remitting multiple sclerosis according to Mac Donald criteria (2010)
* EDSS score at the inclusion from 0 to 4
* With at least 1 symptom of pyramidal injury during clinical exam
* Written informed consent
* Affiliated to a Health Care system

Healthy Volunteers:

* More than 18 years old
* Written informed consent
* Affiliated to a Health Care system

Exclusion Criteria:

Patients

* progressive MS ;
* Corticoids during the last 60 days before inclusion ;
* Other neurological disease or Other progressive systemic disease
* adults subject to legal protection or persons deprived of liberty
* Contraindications to MRI
* Contraindications to motor evoked potentials
* Current pregnancy or breast-feeding

Healthy volunteers:

* History of disease affecting central nervous system
* Familial history of MS
* History of medullar injury
* Spinal osteoarthritis which can lead to a spinal hypersignal ;
* adults subject to legal protection or persons deprived of liberty
* Contraindications to MRI
* Contraindications to motor evoked potentials
* Current pregnancy or breast-feeding

Primary outcomes:
measure: association ratio between EDSS score and focal injury fraction at inclusion
timeFrame: 24 months
Secondary outcomes:
measure: Correlation between focal lesion load and changes in Expanded Disability Status Scale (EDSS)
timeFrame: 24 months
measure: Correlation between the severity of lesions and changes in Expanded Disability Status Scale (EDSS)
timeFrame: 24 months
measure: Differences in central conduction times between patients and healthy volunteers
timeFrame: 1 day
measure: Correlation between focal lesion load and changes in Timed 25-Foot Walk Test (T25W)
timeFrame: 24 months
measure: Correlation between the severity of lesions and changes in Timed 25-Foot Walk Test (T25W)
timeFrame: 24 months
measure: Correlation between focal lesion load and changes in Nine Hole Peg Test (9HPT)
timeFrame: 24 months
measure: Correlation between the severity of lesions and changes in Nine Hole Peg Test (9HPT)
timeFrame: 24 months
measure: Correlation between focal lesion load and changes in walking distance
timeFrame: 24 months
measure: Correlation between the severity of lesions and changes in walking distance
timeFrame: 24 months
measure: Correlation between focal lesion load and changes in 12-Item Multiple Sclerosis Walking Scale (MSWS12) score
timeFrame: 24 months
measure: Correlation between the severity of lesions and all limbs electrophysiology parameters
timeFrame: 24 months
measure: Correlation between in focal lesion load of pathways and changes in Expanded Disability Status Scale
timeFrame: 24 months
Other outcomes:
Locations:
city: Marseille
country: France
facility: AP-HM Timone
city: Rennes
country: France
facility: CHU Rennes
Study officials:
affiliation: Rennes University Hospital
name: Raphael Chouteau, Md
role: PRINCIPAL_INVESTIGATOR
References: