Upregulated serum miR-128-3p in progressive and relapse-free multiple sclerosis patients.

BACKGROUND: Circulating microRNAs have emerged as novel multiple sclerosis (MS) biomarkers. AIMS: To assess the association between candidate miR expression in serum samples of patients with MS and the disease course. METHODS: Serum levels of ten microRNAs (ie, miR-199, miR-128-3p, miR-20a-5p, miR-27a-3p, miR-15b-5p, miR-325, miR-92a1-5p, miR-223-5p, miR-22-5p, and miR-23a-5p) were measured in 74 MS cases and 17 non-MS controls consecutively enrolled at Verona University Hospital. The association of microRNA expression with patients' clinical and MRI features was analyzed. Candidate microRNAs were detected by real-time PCR and expressed as ratio of each microRNA level to a normalizer. RESULTS: Serum miR-128-3p levels were higher in progressive than relapsing MS (median ratio 2.86 vs 0.73, P = .036). In addition, miR-128-3p was upregulated in patients without relapses after sample collection compared to cases who relapsed (1.64 vs 0.82; P = .014). miR-128-3p levels and relapse rate were inversely correlated (r = -.44, P = .008). CONCLUSIONS: Serum levels of mir-128-3p could be related to biological mechanisms underlying MS activity and progression.

Relevance of antibodies to myelin oligodendrocyte glycoprotein in CSF of seronegative cases.

OBJECTIVE: To determine the diagnostic relevance of myelin oligodendrocyte glycoprotein antibodies (MOG-Abs) in CSF of seronegative cases by retrospectively analyzing consecutive time-matched CSF of 80 MOG-Ab-seronegative patients with demyelinating disease. METHODS: The cohort included 44 patients with NMOSD and related disorders and 36 patients with multiple sclerosis (MS). Two independent neurologists blinded to diagnosis analyzed MOG-Abs by live cell-based immunofluorescence assay with goat anti-human immunoglobulin (Ig) G (whole molecule) antibody. Sera were tested at dilutions of 1:20 and 1:40, and a cutoff of 1:160 was considered for serum positivity. CSF specimens were tested undiluted and at 1:2 dilution with further titrations in case of positivity. Anti-IgG-Fc and anti-IgM-µ secondary antibodies were used to confirm the exclusive presence of MOG-IgG in positive cases. CSF of 13 MOG-Abs seropositive cases and 36 patients with neurodegenerative conditions was analyzed as controls. RESULTS: Three seronegative cases had CSF MOG-Abs (4% of the whole cohort or 7% of cases excluding patients with MS, in which MOG-Abs seem to lack diagnostic relevance). In particular, 2 patients with neuromyelitis optica spectrum disorder (NMOSD) and 1 with acute disseminated encephalomyelitis had MOG-Abs in CSF. Analysis with anti-IgG-Fc and anti-IgM confirmed the exclusive presence of MOG-IgG in the CSF of these patients. Among the control group, MOG-Abs were detectable in the CSF of 8 of 13 MOG-Ab-seropositive cases and in none of the patients with neurodegenerative disorders. CONCLUSION: Although serum is the optimal specimen for MOG-Ab testing, analyzing CSF could improve diagnostic sensitivity in seronegative patients. This observation has relevant diagnostic impact and might provide novel insight into the biological mechanisms of MOG-Ab synthesis.

2017 McDonald criteria for multiple sclerosis: Earlier diagnosis with reduced specificity?

BACKGROUND: McDonald criteria for multiple sclerosis (MS) diagnosis were revised in 2017. OBJECTIVE: Aim of our study was to evaluate and compare the sensitivity and specificity of 2017 and 2010 McDonald criteria in patients presenting with an initial demyelinating event (IDE). METHODS: We retrospectively identified patients with an IDE and collected clinical, MRI and CSF data in order to demonstrate fulfilment of 2010 and 2017 McDonald criteria. RESULTS: 2017 McDonald criteria showed 100% (86.8-100%) sensitivity and 13.8% (3.9-31.7%) specificity. CONCLUSION: 2017 McDonald criteria appear to have higher sensitivity but reduced specificity compared to 2010 McDonald criteria.