Abstract

Relapsing-remitting multiple sclerosis (RRMS) is characterised by clinical relapses followed by variable recovery, which may be complete, partial or absent, contributing to the development of irreversible disability. The mechanisms underlying recovery are not yet fully understood, and there is a lack of early prognostic biomarkers. 

The FIS_00002258 study aims to characterise the dynamics of tissue damage and recovery during and after a relapse, investigating the role of brain plasticity and repair processes, and identifying potential biomarkers predictive of clinical outcome. This is a prospective, interventional, non-pharmacological, single-centre, non-profit study, which will include 50 patients with RRMS experiencing a clinical relapse, assessed prior to the start of steroid treatment, 50 patients with stable RRMS and 30 healthy controls matched for age and sex.

Participants will undergo a multimodal assessment comprising sodium (23Na) metabolic magnetic resonance imaging (MRI), myelin imaging, diffusion imaging and resting-state functional MRI, combined with a neurophysiological assessment of long-term potentiation (LTP) using transcranial magnetic stimulation (TMS). 

Serological biomarkers of axonal damage and inflammation will also be analysed, in particular the neurofilament light chain (NF-L) and the neuropeptide AgRP. Patients with a relapse will be assessed at baseline and at 3, 6 and 12 months, whilst healthy controls will be assessed at baseline, at 6 and at 12 months. The integration of neuroimaging, neurophysiological and serological data will enable us to characterise the severity and specificity of tissue damage and to study its evolution over time, assessing the relationship between initial and short-term changes in biomarkers and clinical outcome one year after relapse. 

It is hypothesised that the early onset and rapid resolution of adaptive changes are associated with complete clinical recovery, whilst their persistence may reflect non-adaptive mechanisms. The study therefore aims to elucidate the metabolic, structural, functional, neurophysiological and serological mechanisms involved in tissue repair following a relapse in RRMS. The identification of prognostic biomarkers could help to define the optimal therapeutic window, monitor response to treatment and identify new potential targets for neuroprotective strategies.