Editorial: "Inside-Out" vs "Outside-In" Paradigms in Multiple Sclerosis Etiopathogenesis

Which of the two theories better depicts the very first pathological changes in MS is debated. Since a better evaluation of MS etiopathogenesis could also optimize patients' management, the present issue was aimed to stimulate a discussion about possible overlooked candidates in support of each theory. [...]dysregulation of immune responses, promoted by the genetic background and potentially triggered by environmental factors, could represent the main mechanism in MS onset and progression. Cennamo et al. applied Optical Coherence Tomography to investigate the role of peripapillary vessel density as an early biomarker in MS. This tool was relevant for identifying patients in the earliest phases of MS. Todea et al. showed how magnetic resonance imaging (MRI) enables identification of focal demyelination in white matter and cortical lesions already from the earliest phases of MS. Lesion burden was associated with serum neurofilament light chain (sNfL) levels, a biomarker of axonal injury. [...]the 2-year longitudinal changes of cortical and white matter lesion burden correlated with the cognitive performances of MS patients.