The Inflammatory Process and the Medical Imaging in Patients With an Inflammatory Disease of the Central Nervous System.

While significant progress has been made on medical imagery in recent years in the individualization of different lesions in the nervous system for demyelination, axonal loss, atrophy, little progress has been made in the specific recognition the inflammatory process. Yet this point is essential since the currently available treatments have a partial impact mainly on the inflammatory component and that many uncertainties remain about the links between inflammation and tissue destruction affecting myelin and axons. The recent discovery of a macrophage cell marker in the CNS, more specific (USPIO) of inflammation gives us the opportunity to answer important questions which one can sense that this could have a significant impact on therapeutic drug monitoring of these patients. This study will involve 50 patients recruited in five French centers (Marseille, Paris, Reims, Rennes, Toulouse) from the earliest manifestations of the disease with clinical and MRI scheduled for the first 3 years of their disease.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system affecting 60.000 persons in France and characterized by widespread inflammation, focal demyelination, and a variable degree of axonal loss. In recent years the concept of MS as an inflammatory neurodegenerative disease has been corroborated by neuropathologic and in vivo MR imaging studies. A number of MR studies show that the principal pathological substrate of permanent disability is axonal loss as detected in MR studies as global atrophy, but also regionally in the white or grey matter, and that atrophy already occurs at early stages of the disease. Though MR imaging is a powerful tool for MS in terms of diagnosis, description of the natural history of the disease and treatment monitoring, the major drawback of MRI in MS is the lack of specificity of the MR findings. Furthermore, with the advent of disease modifying drugs, there is a need for robust and specific MR markers to identify e.g. clinically isolated syndrome (CIS) patients at presentation at high risk to develop MS or a more severe disease course. An increasing body of MRI evidence corroborates that CIS show early and dynamic changes detected by MR imaging, such as global or regional brain atrophy, as a sign of progressive axonal loss, but atrophy is already a late stage sign of the disease, when tissue is lost. Considerable efforts are spent today to identify early and prognostic MR markers for high risk CIS patients. In the current project we endeavour to study CIS patients with inflammatory disease of the central nervous system or early clinical deficit by using cell labelling MR imaging with ultra small superparamagnetic iron oxide particles (USPIO), which specifically label blood-borne macrophages, a key cell population in MS. We hypothesise that number/volume of USPIO (SH U 555 C) enhancement during the first year is a predictive marker for high risk CIS patients at presentation. This hypothesis is in line with recent findings in the animal model of MS, EAE. Secondary measures of this study will include comparison of the USPIO (SH U 555 C) findings with other highly sensitive, but non-specific MR parameters.