Motor Asymmetry in Progressive Multiple Sclerosis Patients

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.