Project Rational

A better understanding of the causes of physical disability is an important unmet need in progressive Multiple Sclerosis patients. Progressive Multiple Sclerosis patients most often present a worsening pyramidal syndrome of lower and, to a lesser extent, upper limbs (Lublin et al., 2014) suggesting a strong corticospinal tract involvement. The systematic high resolution Magnetic Resonance Imaging exploration of lesions location and severity, as well as extra-lesional tissue, on pan-medullar and encephalic motor tracts offers the opportunity to better understand the pathological mechanism associated with motor impairment.

Scientific aims

This project will follow a twofold approach. First, the investigators will consider an "inter-patient" approach where independent and absolute Magnetic Resonance metrics for each limb will be related to disability. Second, the investigators will consider an "intra-patient" approach (i.e. comparing differences of Magnetic Resonance metric and of clinical score from the left and the right side in the same patient). For this purpose, progressive Multiple Sclerosis patients with asymmetric motor impairment will be studied. Confronting clinical and Magnetic Resonance Imaging metric value asymmetries indeed offers the unique opportunity to free oneself from many confounding factors such as genetics, age, duration of disease evolution, acquisition bias, etc. These two approaches will allow us to precisely study the impact of local factors such as Multiple Sclerosis lesions located on motor tracts on motor disability.

Methodology

The investigators propose an observational multicenter cross-sectional and prognostic study. This study will involve two French centers (Rennes, Marseille) and will include a total of 40 progressive Multiple Sclerosis patients with an asymmetrical motor deficit. Twenty sex and age matched controls will be needed to calibrate quantitative Magnetic Resonance imaging (magnetization transfer ratio). Encephalic and pan medullar structural and quantitative Magnetic Resonance images will be acquired at inclusion and clinical follow-up examinations will be performed at inclusion and 24 months. Detailed motor evaluation "per limb" will be performed, including the motor American Society Injury. Association sub-score and upper and lower limbs muscle strength measurements using a dynamometer.

1. - Inclusion Criteria:

   1.1/ Patients:

   • Aged between 18 and 60 years.
   • Primary Progressive Multiple Sclerosis or Secondary Progressive Multiple Sclerosis as defined by Mac Donald revised criteria in 2017.
   • Expanded Disability Status Scale lower or equal to 8.0, at inclusion.
   • asymmetric motor deficit. The motor deficit asymmetry will be defined by a difference of 3 or more at the American Society Injury. Association motor sub-score per limb between the right lower limb and the left lower limb.
   • No evidence of focal inflammatory activity for at least 3 years (no clinical relapse, no gadolinium enhancement on an Magnetic Resonance Imaging scan and no new T2 lesion)
   • Provided written informed consent according to the Institutional review board approval
   • Affiliated to the French healthcare system.

   1.2 / Controls:

   • Aged between 18 and 60 years, sex and age matched with patients.
   • Provided written informed consent according to the Institutional review board approval
   • Affiliated to the French healthcare system.

2. - Non-inclusion criteria:

2.1 /Patients:

• cerebellar Expanded Disability Status Scale sub score higher than pyramidal Expanded Disability Status Scale sub score.
• Relapse or corticosteroids in the 30 days preceding inclusion.
• Other neurological diseases.
• Lack of ability to understand the Institutional review board consent form.
• Magnetic Resonance contraindications.
• Pregnancy and breastfeeding.
• Major persons subject to legal protection (legal safeguards, guardianship,curatorship), persons deprived of their liberty

2.2 / Controls:

• Personal history of central nervous related disease
• Familial history of Multiple Sclerosis.
• Personal history of spinal cord injury.
• Personal history of spondylotic myelopathy.
• Magnetic Resonance Imaging contraindication.
• Lack of ability to understand the Institutional review board form.
• Major persons subject to legal protection (legal safeguards, guardianship, curatorship), persons deprived of their liberty
• Pregnancy and breastfeeding.

Patient population will consist of progressive Multiple Sclerosis patients (both Primary Progressive Multiple Sclerosis and Secondary Progressive Multiple Sclerosis), a population for whom a better understanding of the causes of disability is an unmet need.