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• One sNFL dosage highlights patients worth of further clinical in-depth analysis. • Careful therapy tailoring ensures low biologically-evident levels of inflammation. • sNFL remains always informative along the whole disease course. In the field of research for new validated surrogate biomarkers of treatment efficacy, disease activity and progression in Multiple Sclerosis (MS), serum neurofilament light-chain (sNFL) are actually the best candidate for MS patient monitoring. However, before they can be implemented in clinical practice, their usefulness as additional red flag routine measure must be demonstrated. To tackle the problem, this real-life cross-sectional study at the Regional Referring Center for Multiple Sclerosis (CRESM) aims to characterize sNFL levels and prevalence of elevated sNFL, according to our age-dependent cut-off values, in a large group of patients with different types of MS and treatment conditions. 908 serum samples from as many MS patients being admitted at CRESM for diagnostic definition and/or during routinary treatment monitoring were consecutively collected between January 2019 and January 2020. sNFL levels were measured by single molecule array (Simoa™) technology on SR-X instrument using NF-light assays (Quanterix); results were interpreted using previously published cut-off values. Primary and Secondary Progressive MS (PPMS, SPMS) forms demonstrate higher levels and prevalence of elevated sNFL (PPMS= 32 %, SPMS= 21 %) compared to the Relapse and Remitting one (RRMS = 12 %). Besides, naïve samples of RRMS and PPMS subtypes showed higher prevalence of elevated sNFL (RRMS naïve= 31 %, PPMS naïve=67 %) compared to samples from patients treated for more than 12 months (RRMS treat>12m= 9 %, PPMS treat>12m= 19 %); treated SPMS patients demonstrated higher sNFL levels and a prevalence (22 %) of elevated sNFL compared to RRMS treated patients. Focusing on RRMS, no statistical difference was found between groups of patients treated for whatever time (up to or more than 60 months) and with either DMT type (high or low-efficacy DMT). Finally, RRMS patients treated with all DMTs for more than 12 months, with the exception of teriflunomide and alemtuzumab showed a prevalence of elevated sNFL in the range of 5–10 %. in a real-world setting comprising about 1000 MS patients, sNFL quantification was elevated in 5-to-67 % of patients, in different MS forms and treatment conditions. Elevated levels of sNFL must be considered a red-flag suggesting the need of a further clinical monitoring in any circumstance, as it can be indicative of new inflammation, ongoing degeneration or co-morbidities. This study supports the introduction of sNFL quantification in everyday patient management. [ABSTRACT FROM AUTHOR]

Fatigue is one of the most distressing symptoms of Multiple Sclerosis, impairing quality of life, work performance and social interactions. Moreover, it is difficult to objectively assess, and is often evaluated via subjective questionnaire; however, objective metrics are highly desirable. Objective of this paper is to implement a differential fatigue measure based on evoked potentials, and assess its reliability and coherence with walking tests and subjective questionnaires. Method: the Regional Multiple Sclerosis Reference Centre, San Luigi Gonzaga Hospital, Italy, is carrying out tests in order to assess the effectiveness of 4-amino-pyridine for fatigue relief. This work takes as input evoked potential waveforms and implements an algorithm to perform suitable signal processing and provide a fatigue index and a related reliability metric. This information is put in relationship with the walking test results and the subjective fatigue scores. Preliminary results reveal that fatigue measures based on evoked potentials, subject to proper data processing, are not always coherent with subjective questionnaires and walking tests. This may be due to the fact that fatigue cannot be reduced to a mere muscular/conduction problem, and the walking tests are heavily conditioned by the disability degree. Moreover, the reliability of such measures carries not trivial information that should be carefully considered. As a conclusion, evoked potentials and gait analysis represent a good complement of subjective questionnaires as for fatigue assessment. The significance of our work lies in the fact that reliable fatigue measures can help improving the patients' quality of life, allowing assessment of the therapy effectiveness and posology. [ABSTRACT FROM AUTHOR]