Background: Serum neurofilament light (sNfL) chain is a promising biomarker reflecting neuro-axonal injury in multiple sclerosis (MS). However, the ability of sNfL to predict outcomes in real-world MS cohorts requires further validation. Objective: The aim of the study is to investigate the associations of sNfL concentration, magnetic resonance imaging (MRI) and retinal optical coherence tomography (OCT) markers with disease worsening in a longitudinal European multicentre MS cohort. Methods: MS patients ( n = 309) were prospectively enrolled at four centres and re-examined after 2 years ( n = 226). NfL concentration was measured by single molecule array assay in serum. The patients’ phenotypes were thoroughly characterized with clinical examination, retinal OCT and MRI brain scans. The primary outcome was disease worsening at median 2-year follow-up. Results: Patients with high sNfL concentrations (⩾8 pg/mL) at baseline had increased risk of disease worsening at median 2-year follow-up (odds ratio (95% confidence interval) = 2.8 (1.5–5.3), p = 0.001). We found no significant associations of MRI or OCT measures at baseline with risk of disease worsening. Conclusion: Serum NfL concentration was the only factor associated with disease worsening, indicating that sNfL is a useful biomarker in MS that might be relevant in a clinical setting.

BackgroundThere is limited evidence regarding optimal duration of antibiotic treatment in neuroborreliosis. We aimed to compare efficacy and safety of oral doxycycline for 2 and 6 weeks in European Lyme neuroborreliosis (LNB).MethodsThe trial had a randomised, double-blinded, placebo-controlled, non-inferiority design. Patients with LNB were recruited from eight Norwegian hospitals and randomised to doxycycline 200 mg once daily for 2 weeks, followed by 4 weeks of placebo, or doxycycline 200 mg once daily for 6 weeks. The primary endpoint was clinical improvement as measured by difference in a Composite Clinical Score (0–64 points) from baseline to 6 months. The non-inferiority margin was predetermined to 0.5 points.ResultsOne hundred and twenty-one patients were included. Fifty-two treated for 2 weeks and 53 for 6 weeks were included in the intention-to-treat analyses, and 52 and 51 in per-protocol analysis. Mean difference in clinical improvement between the groups was 0.06, 95% CI −1.2 to 1.2, p=0.99 in the intention-to-treat population, and −0.4, 95% CI −1.4 to 0.7, p=0.51 in the per-protocol population and non-inferiority could not be established. There were no treatment failures and no serious adverse events. The groups did not differ in secondary outcomes including clinical scores at 10 weeks and 12 months, cerebrospinal fluid data and patient-reported outcome measures. Patients receiving 6 weeks doxycycline reported slightly more side effects in week 5.ConclusionOur results strongly indicate that there are no benefits of doxycycline treatment beyond 2 weeks in European LNB.Trial registration number2015-001481-25.

Background and Goals: Multiple sclerosis (MS) is a central nervous system inflammatory disease where magnetic resonance imaging (MRI) is an important tool for diagnosis and disease monitoring. Quantitative measurements of lesion volume, lesion count, distribution of lesions, and brain atrophy have a potentially significant value for evaluating disease progression. We hypothesize that utilizing software designed for evaluating MRI data in MS will provide more accurate and detailed analyses compared to the visual neuro-radiological evaluation.Methods: A group of 56 MS patients (mean age 35 years, 70% females and 96% relapsing-remitting MS) was examined with brain MRI one and 5 years after diagnosis. The T1 and FLAIR brain MRI sequences for all patients were analyzed using the LesionQuant (LQ) software. These data were compared with data from structured visual evaluations of the MRI scans performed by neuro-radiologists, including assessments of atrophy, and lesion count. The data from LQ were also compared with data from other validated research methods for brain segmentation, including assessments of whole brain volume and lesion volume. Correlations with clinical tests like the timed 25-foot walk test (T25FT) were performed to explore additional value of LQ analyses.Results: Lesion count assessments by LQ and by the neuro-radiologist were significantly correlated one year (cor = 0.92, p = 2.2 × 10−16) and 5 years (cor = 0.84, p = 2.7 × 10−16) after diagnosis. Analyzes of the intra- and interrater variability also correlated significantly (cor = 0.96, p < 0.001, cor = 0.97, p < 0.001). Significant positive correlation was found between lesion volume measured by LQ and by the software Cascade (cor = 0.7, p < 0.001. LQ detected a reduction in whole brain percentile >10 in 10 patients across the time-points, whereas the neuro-radiologist assessment identified six of these. The neuro-radiologist additionally identified five patients with increased atrophy in the follow-up period, all of them displayed decreasing low whole brain percentiles (median 11, range 8–28) in the LQ analysis. Significant positive correlation was identified between lesion volume measured by LQ and test performance on the T25FT both at 1 and 5 years after diagnosis.Conclusion: For the number of MS lesions at both time-points, we demonstrated strong correlations between the assessments done by LQ and the neuro-radiologist. Lesion volume evaluated with LQ correlated with T25FT performance. LQ-analyses classified more patients to have brain atrophy than the visual neuro-radiological evaluation. In conclusion, LQ seems like a promising supplement to the evaluation performed by neuro-radiologists, providing an automated tool for evaluating lesions in MS patients and also detecting early signs of atrophy in both a longitudinal and cross-sectional setting.