The risk of conversion from a clinically isolated syndrome to multiple sclerosis was significantly lower with minocycline than with placebo over 6 months but not over 24 months. (Funded by the Multiple Sclerosis Society of Canada; ClinicalTrials.gov number, NCT00666887 .).

In contrast to depression in the general population, depression in MS is largely chronic, which suggests a different pathophysiology.

Background: Recent evidence suggests a role for the gut–brain axis in the pathophysiology of multiple sclerosis (MS). Materials and methods: We studied biomarkers of intestinal permeability in 126 people with MS (57 relapsing-remitting multiple sclerosis (RRMS) and 69 progressive MS) and in a group of healthy controls for comparison. Serum/plasma concentrations of zonulin (a regulator of enterocyte tight junctions), tight junction proteins (ZO-1 and occludin), intestinal fatty acid binding protein (IFABP)/ileal bile acid binding protein (IBABP), D-lactate, and lipopolysaccharide (LPS) binding protein were measured. Results: Zonulin concentrations were significantly higher when a concurrent magnetic resonance imaging (MRI) confirmed the presence of blood–brain barrier (BBB) disruption (Gad+ RRMS) and were correlated with tight junction proteins. IBABP and D-lactate were elevated in people with RRMS compared to controls, but did not discriminate between Gad+ and Gad– subgroups. Baseline zonulin concentrations were associated with 1-year disease progression in progressive MS. Conclusions: People with MS have altered biomarkers of intestinal barrier integrity. Zonulin concentrations are associated with 1-year disease progression in progressive MS and closely mirror BBB breakdown in RRMS. Zonulin may mediate breakdown of both the intestinal barrier and the BBB in gut dysbiosis through the regulation of tight junctions. This could explain how the gut–brain axis modulates neuroinflammation in MS.

Eighteen years ago, the severe acute respiratory syndrome (SARS) experience 1-5 highlighted limited knowledge of early treatments for novel pandemic respiratory viruses. With the emergence of SARS-CoV-2, early experience in Wuhan, 6 the Lombardy region of Italy 7,8 and New York City 9 demonstrated the need to suppress severe disease to prevent health system collapse. Hydroxychloroquine, derived from the centuries-old antimalarial medicine quinine, has broad antiviral effects and immunomodulatory properties, making it an attractive candidate to be repurposed for SARS-CoV-2 infection. The precise mechanisms of immunomodulation are uncertain, but the net result is inhibition of macrophage production of proinflammatory cytokines tumor necrosis factor (TNF)-α and Assessing the efficacy and safety of hydroxychloroquine as outpatient treatment of COVID-19: a randomized controlled trial