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Objective: To describe the profile of patients with multiple sclerosis (MS) treated with fingolimod in Spain and to assess the effectiveness and safety of fingolimod after 4 years of inclusion in the Spanish Gilenya Registry. Methods: An observational, retrospective/prospective, multicenter case registry, including all patients with relapsing-remitting MS (RRMS) starting treatment with fingolimod in 43 centers in Spain. Analyses were performed in the overall population and in subgroups according to prior disease-modifying therapy (DMT): glatiramer acetate/interferon beta-1 (BRACE), natalizumab, other treatment, or naïve. Results: Six hundred and sixty-six evaluable patients were included (91.1% previously treated with at least one DMT). The mean annualized relapse rate (ARR) prior to fingolimod was 1.12, and the mean EDSS at fingolimod initiation was 3.03. Fingolimod reduced the ARR by 71.4%, 75%, 75.5%, and 80.3%, after 1, 2, 3 and 4 years, respectively (p<0.001). This significant reduction in the ARR continued to be observed in all subgroups. After 4 years, the EDSS showed a minimal deterioration, with the EDSS scores from year 1 to year 4 remaining mostly stable. The percentage of patients without T1 Gd+ lesions progressively increased from 45.6% during the year prior to fingolimod initiation to 88.2% at year 4. The proportion of patients free from new/enlarged T2 lesions after 4 years of fingolimod treatment was 80.3%. This trend in both radiological measures was also observed in the subgroups. Adverse events (AEs) were experienced by up to 41.6% of patients (most commonly: lymphopenia [12.5%] and urinary tract infection [3.7%]). Most AEs were mild in severity, 3.6% of patients had serious AEs. Conclusions: The patient profile was similar to other observational studies. The results obtained from the long-term use of fingolimod showed that it was effective, regardless of prior DMT, and it had adequate safety results, with a positive benefit-risk balance. [ABSTRACT FROM AUTHOR]

Keywords: cognition; metabolomics; metagenomics; microbiome; Saccharomyces cerevisiae EN cognition metabolomics metagenomics microbiome Saccharomyces cerevisiae 740 743 4 09/03/21 20210901 NES 210901 There is progressive awareness that gut microbiota composition and function are associated with cognitive traits [1] through a putative gut microbiota-brain axis. Cognition, metabolomics, metagenomics, microbiome, Saccharomyces cerevisiae 8 Teoh ST, Putri S, Mukai Y, Bamba T, Fukusaki E. A metabolomics-based strategy for identification of gene targets for phenotype improvement and its application to 1-butanol tolerance in Saccharomyces cerevisiae. [Extracted from the article]

Background and purpose: Oral or intravenous methylprednisolone (≥500 mg/day for 5 days) is recommended for multiple sclerosis (MS) relapses. Nonetheless, the optimal dose remains uncertain. We compared clinical and radiological effectiveness, safety and quality of life (QoL) of oral methylprednisolone [1250 mg/day (standard high dose)] versus 625 mg/day (lesser high dose), both for 3 days] in MS relapses. Methods: A total of 49 patients with moderate to severe MS relapse within the previous 15 days were randomized in a pilot, double‐blind, multicentre, non‐inferiority trial (ClinicalTrial.gov, NCT01986998). The primary endpoint was non‐inferiority of the lesser high dose by Expanded Disability Status Scale (EDSS) score improvement on day 30 (non‐inferiority margin, 1 point). The secondary endpoints were EDSS score change on days 7 and 90, changes in T1 gadolinium‐enhanced and new/enlarged T2 lesions on days 7 and 30, and safety and QoL results. Results: The primary outcome was achieved [mean (95% confidence interval) EDSS score difference, −0.26 (−0.7 to 0.18) at 30 days (P = 0.246)]. The standard high dose yielded a superior EDSS score improvement on day 7 (P = 0.028). No differences were observed in EDSS score on day 90 (P = 0.352) or in the number of T1 gadolinium‐enhanced or new/enlarged T2 lesions on day 7 (P = 0.401, 0.347) or day 30 (P = 0.349, 0.529). Safety and QoL were good at both doses. Conclusions: A lesser high‐dose oral methylprednisolone regimen may not be inferior to the standard high dose in terms of clinical and radiological response. [ABSTRACT FROM AUTHOR]

Background and purpose: Chitinase 3‐like 1 (CHI3L1) and neurofilament light chain (NF‐L) are promising biomarkers of disability in multiple sclerosis (MS). However, their role in cognitive dysfunction remains elusive. Here, we aimed to correlate cerebrospinal fluid (CSF) levels of CHI3L1 and NF‐L with cognitive status in MS. Methods: Fifty one recently diagnosed patients were cognitively evaluated and CSF was collected. Levels of CHI3L1 and NF‐L were determined by ELISA. Spearman's partial correlation coefficient was performed. Results: After adjusting cognitive scores by age, anxiety and EDSS, association was detected between CHI3L1 levels and Trail Making Test A (rs = 0.348; p = 0.016) and between NF‐L levels and Word List Generation (rs = −0.324; p = 0.025). Conclusion: High levels of CSF CHI3L1 and NF‐L are associated with cognitive impairment in the early phases of MS. [ABSTRACT FROM AUTHOR]

Paroxysmal dystonia is an uncommon but well-established feature of multiple sclerosis (MS). Attacks can occur in established MS and may even occasionally be the initial symptom of this disorder. Pathological laughter is usually seen as a pseudobulbar palsy in some diffuse neurological diseases, but cases have been described, mostly in ischaemic attacks or tumours, where it is presented as bursts of laughter of variable duration. The pathogenesis of neither of the two phenomena has been fully established but both have been reported as being positive phenomena resulting from ectopic activation with ephaptic spread. We describe the first reported case of a paroxysmal hemidystonia together with bursts of pathological laughter as the first manifestation of MS. [ABSTRACT FROM AUTHOR]

Objectives: To establish whether magnetisation transfer ratio (MTR) histograms are sensitive to change in normal appearing grey matter (NAGM) in early relapsing-remitting multiple sclerosis (RRMS) in the absence of significant disability; and to assess whether grey or white matter MTR measures are associated with clinical measures of impairment in early RRMS METHODS: 38 patients were studied (mean disease duration 1.9 years (range 0.5 to 3.7); median expanded disability status scale (EDSS) 1.5 (0 to 3)), along with 35 healthy controls. MTR was determined from proton density weighted images with and without MT presaturation. SPM99 was used to generate normal appearing white matter (NAWM) and NAGM segments of the MTR map, and partial voxels were minimised with a 10 pu threshold and voxel erosions. Mean MTR was calculated from the tissue segments. Atrophy measures were determined using a 3D fast spoiled gradient recall sequence from 37 patients and 17 controls.Results: Mean NAGM and NAWM MTR were both reduced in early RRMS (NAGM MTR: 31.9 pu in patients v 32.2 pu in controls; p<0.001; NAWM MTR: 37.9 v 38.3 pu, p = 0.001). Brain parenchymal fraction (BPF) correlated with NAGM MTR, but when BPF was included as a covariate NAGM MTR was still lower in the patients (p = 0.009). EDSS correlated with NAGM MTR (r = 0.446 p = 0.005).Conclusions: In early RRMS, grey matter MTR abnormality is apparent. The correlation with mild clinical impairment (in this essentially non-disabled cohort) suggests that NAGM MTR could be a clinically relevant surrogate marker in therapeutic trials. [ABSTRACT FROM AUTHOR]