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The proportion of patients with clinically isolated syndrome (CIS) reported to convert to clinically definite multiple sclerosis varied between 30 and 75%. We studied the lifetime probability of remaining in the “CIS only” condition. The study was based on the longitudinally followed Gothenburg 1950–1964 incidence cohort (n = 306). Survival analysis revealed that 17.8% of 236 attack onset patients remained “CIS only”. Patients with afferent (optic and sensory) symptoms had a better prognosis with approximately 30% of these patients remaining “CIS only”. Patients who had experienced no relapse during the first 25 years remained “CIS only” for the subsequent 25 years of follow-up. [ABSTRACT FROM AUTHOR]

Background: Serum neurofilament light (sNfL) reflects neuroaxonal damage and is now used as an outcome in treatment trials of relapsing-remitting multiple sclerosis (RRMS). However, the diagnostic properties of sNfL for monitoring disease activity in individual patients warrant further investigations. Method: Patients with suspected relapse and/or contrast-enhancing lesions (CELs) were consecutively included and performed magnetic resonance imaging (MRI) of the brain at baseline and weeks 28 and 48. Serum was obtained at baseline and 2, 4, 8, 16, 24, and 48 weeks. Neurofilament light concentration was measured using Single molecule array technology. Results: We included 44 patients, 40 with RRMS and 4 with clinically isolated syndrome. The median sNfL level peaked at 2 weeks post-baseline (14.6 ng/L, interquartile range (IQR); 9.3–31.6) and reached nadir at 48 weeks (9.1 ng/L, IQR; 5.5–15.0), equivalent to the median sNfL of controls (9.1 ng/L, IQR; 7.4–12). A baseline Z -score of more than 1.1 (area under the curve; 0.78, p < 0.0001) had a sensitivity of 81% and specificity of 70% to detect disease activity. Conclusion: One out of five patients with relapse and/or CELs did not change significantly in post-baseline sNfL levels. The utility of repeated sNfL measurements to monitor disease activity is complementary rather than a substitute for clinical and MRI measures. [ABSTRACT FROM AUTHOR]

Mucosal-associated invariant T (MAIT) cells are innate-like T cells comprising up to 10% of the peripheral blood T cells in humans. During ontogeny, MAIT cells can first be detected in the cord blood in low amounts, but rise steadily after birth. In this population-based study, we show that their counts continue to increase, reaching maximal levels (4.5% of CD3+ cells, 65 cells/ll) in the third and fourth decenniums. At this age, the amounts of MAIT cells exhibit the highest interindividual variability. The values then dramatically decline; subjects 80 years old and older have on average 10 times less MAIT cells, both absolutely and as a percentage among CD3+ T cells, than subjects in fertile age. The senescence of MAIT cells is associated with decreased CD8/double negative (DN) ratio. Finally, we observed significantly higher amounts of MAIT cells in women of reproductive age than in men of the same age. Our data suggest that further studies aimed at elucidating a role of MAIT cells in human pathologies must recruit age- and gender-matched controls. [ABSTRACT FROM AUTHOR]

Background and purpose: Breakthrough disease on first‐line injectables in relapsing‐remitting multiple sclerosis (RRMS) is a common clinical situation where comparative studies between different escalation therapies are lacking. The aim of this study was to compare the efficacy, safety and medication persistence of natalizumab (NTZ), rituximab (RTX) and fingolimod (FGL) as escalation therapy in RRMS. Methods: Patients switching from interferon or glatiramer acetate to NTZ, RTX or FGL due to breakthrough disease were identified through the Swedish multiple sclerosis (MS) registry at four large MS centers in this retrospective observational study. Data were collected from the MS registry and medical charts. Hazard ratios (HRs) for relapses, adverse events and drug discontinuation with 95% confidence interval (CI) were calculated using multivariable confounder‐adjusted Cox proportional hazard models. Results: A total of 241 patients were included. The annualized relapse rates were 0.02 for NTZ, 0.03 for RTX and 0.07 for FGL. Compared with NTZ, the adjusted HR for relapse was 1.0 (95% CI, 0.2–5.6) for RTX and 3.4 (95% CI, 1.3–9.2) for FGL. The annualized drug discontinuation rates were 0.15, 0.01 and 0.15 for NTZ, RTX and FGL, respectively. The adjusted HR for drug discontinuation was 0.05 (95% CI, 0.01–0.38) for RTX and 1.0 (95% CI, 0.6–1.7) for FGL vs. NTZ. Conclusions: In patients with RRMS on interferon/glatiramer acetate with breakthrough disease, switching to NTZ or RTX was associated with less disease activity compared with FGL. RTX displayed superior medication persistence compared with both NTZ and FGL. [ABSTRACT FROM AUTHOR]

Objectives: Methods to evaluate the relative contributions of demyelination vs axonal degeneration over the long‐term course of MS are urgently needed. We used magnetic resonance diffusion tensor imaging (DTI) to estimate degrees of demyelination and axonal degeneration in the corpus callosum (CC) in cases of MS with different final outcomes. Materials and methods: We determined DTI measures mean diffusivity (MD), fractional anisotropy (FA), and axial (AD) and radial (RD) diffusivities in the CC of 31 MS patients, of whom 13 presented a secondary progressive course, 11 a non‐progressive course, and seven a monophasic course. The study participants were survivors from an incidence cohort of 254 attack‐onset MS patients with 50 years of longitudinal follow‐up. As reference, we included five healthy individuals without significant morbidity. Results: In patients with secondary progression, compared to all other groups, the corpus callosum showed increased RD and reduced FA, but no change in AD. None of the parameters exhibited differences among non‐progressive and monophasic course groups and controls. Conclusion: Increased RD was observed in secondary progressive MS, indicating significant myelin loss. Normal RD values observed in the clinically isolated syndrome and non‐progressive groups confirm their benign nature. AD was not a characterizing parameter for long‐term outcome. Demyelination revealed by increased RD is a distinguishing trait for secondary progression. [ABSTRACT FROM AUTHOR]