Systemic inflammation and blood–brain barrier abnormality in relapsing–remitting multiple sclerosis

Abstract Background Systemic inflammation can affect disease expression in multiple sclerosis. The mechanism might involve blood–brain barrier disruption. We aimed to assess the effects of systemic inflammation on disease progression in multiple sclerosis and the role of blood–brain barrier disruption. Methods We recruited adults with relapsing–remitting multiple sclerosis and healthy controls from the general population. Three-dimensional dynamic-contrast enhanced MRI was used to measure blood–brain barrier permeability in the normal-appearing white matter (NAWM). Urinary neopterin, a product of activated macrophages, was measured to provide a readout of systemic inflammation. All study activities were performed in University Hospital Southampton after ethics approval (REC 12/SC/0176). Findings 12 patients with mutliple sclerosis and 12 healthy controls were recruited. Blood–brain barrier permeability in NAWM, measured as the constant Ktrans, was significantly higher in patients than in controls (mean 0·024 ml/100g per min [SD·0·018] vs 0·006 [0·004], p=0·015). Systemic inflammatory activity, measured as the urinary neopterin:creatinine ratio (UNCR), was also significantly higher (3·35 [1·98] vs 1·36 [0·29], p=0·002). Across all participants, there was a weak positive correlation between Ktrans and UNCR ( r =0·40, p=0·031). Interpretation Our findings support the hypothesis that the effects of systemic inflammation on expression of multiple sclerosis disease are mediated by blood–brain barrier disruption. Targeting this disruption and systemic inflammation might provide novel avenues for disease-modifying therapy. Funding University of Southampton, National Institute for Health Research, Multiple Sclerosis Society.