Multiple sclerosis: Inflammation, autoimmunity and plasticity.

In recent years, experimental studies have clarified that immune system influences the functioning of the central nervous system (CNS) in both physiologic and pathologic conditions. The neuro-immune crosstalk plays a crucial role in neuronal development and may be critically involved in mediating CNS response to neuronal damage. Multiple sclerosis (MS) represents a good model to investigate how the immune system regulates neuronal activity. Accordingly, a growing body of evidence has demonstrated that increased levels of pro-inflammatory mediators may significantly impact synaptic mechanisms, influencing overall neuronal excitability and synaptic plasticity expression. In this chapter, we provide an overview of preclinical data and clinical studies exploring synaptic functioning noninvasively with transcranial magnetic stimulation (TMS) in patients with MS. Moreover, we examine how inflammation-driven synaptic dysfunction could affect synaptic plasticity expression, negatively influencing the MS course. Contrasting CSF inflammation together with pharmacologic enhancement of synaptic plasticity and application of noninvasive brain stimulation, alone or in combination with rehabilitative treatments, could improve the clinical compensation and prevent the accumulating deterioration in MS.