Skin sodium is increased in male patients with multiple sclerosis and related animal models

Novel MRI techniques allow a noninvasive quantification of tissue sodium and reveal the skin as a prominent compartment of sodium storage in health and disease. Since multiple sclerosis (MS) immuno-pathology is initiated in the periphery and increased sodium con-centrations induce proinflammatory immune cells, the skin represents a promising compartment linking high sodium concentrations and MS immunopathology. We used a 7-T sodium MRI (Na-23-MRI) and inductively coupled plasma mass spectrometry to investigate the skin sodium content in two mouse models of MS. We additionally performed 3-T Na-23-MRI of calf skin and muscles in 29 male relapsing-remitting MS (RRMS) patients and 29 matched healthy controls. De-mographic and clinical information was collected from interviews, and disease activity was assessed by expanded disability status scale scoring. Na-23-MRI and chemical analysis demonstrated a significantly increased sodium content in the skin during experimental autoim-mune encephalomyelitis independent of active immunization. In male patients with RRMS, Na-23-MRI demonstrated a higher sodium signal in the area of the skin compared to age-and biological sex-matched healthy controls with higher sodium, predicting future disease activity in cranial MRI. In both studies, the sodium enrichment was specific to the skin, as we found no alterations of sodium signals in the muscle or other tissues. Our data add to the recently identified importance of the skin as a storage compartment of sodium and may further represent an important organ for future investigations on salt as a proin-flammatory agent driving autoimmune neuroinflammation such as that in MS.

Automated summary

Novel MRI techniques reveal the skin as a significant compartment of sodium storage in health and disease, with potential links to MS immunopathology. Increased sodium content in skin, as detected by Na-23-MRI, may predict future disease activity in male patients with RRMS. The skin's role as a storage compartment for sodium and its potential implications in autoimmune neuroinflammation, such as in MS, warrant further investigation.