The Silent Disease Activity of Multiple Sclerosis

The concept of “silent” disease activity as a hallmark of the disease even in the earliest phase and during the disease-modifying treatment, is emerging in the last few years. It describes those patients that, even in the absence of classical clinical/radiological events, have an insidious disease activity which is unnoticed by the patient or physician in the early phase of the disease, whereas it becomes clinically relevant later on disease course. This could be mainly characterized by neurodegenerative mechanisms rather than inflammatory disease activity and its measure is fairly beyond the sensitivity of the conventional MRI. One of the expressions of such silent activity may be a surface-in gradient of cortical, thalamic and spinal cord grey matter damage, which is a primary key component of the demyelination and neurodegeneration processes and provides the best clinical correlate in terms of long term disability accumulation. A second emerging relevant sign of silent activity is represented by the chronic active lesions which have been neuropathologically and radiologically well described and which have been proposed as one of the major determinants of disability progression.

According to this evidence, the unique use of No Evidence of Disease Activity (NEDA) status (no relapses, no new T2 and/or Gd-enhancing lesions, no EDSS change) is not completely appropriate to identify patients at high risk of a severe clinical outcome. The main goal of this symposium will be to better elucidate the most relevant molecular and radiological biomarkers of silent disease activity with special focus on Neuropathological, Imaging and CSF data.