Background: Neurofilament light chain protein (NFL) and chitinase3-like1 (CHI3L1) have gained importance recently as prognostic biomarkers in multiple sclerosis (MS).Objectives: We aimed to investigate NFL and CHI3L1 cerebrospinal fluid (CSF) profiles in multiple sclerosis and the informative and prognostic potential of the individual and combined measures.Methods: CSF NFL and CHI3L1 levels were measured in a cross-sectional cohort of 157 MS patients [99 relapsing-remitting (RRMS), 35 secondary progressive (SPMS), and 23 primary progressive (PPMS)]. Clinical relapse and/or gadolinium-enhanced lesions (GEL) in MRI within 90 days from CSF collection by lumbar puncture (LP) were registered and considered as indicators of disease activity. Longitudinal treatment and disability data were evaluated during medical visits with a median follow-up of 50 months.Results: CSF levels of NFL and CHI3L1 were higher in MS patients compared to non-MS controls. In RRMS and SPMS patients, increased NFL levels were associated with clinical relapse, and gadolinium-enhanced lesions in MRI (p < 0.001), while high CHI3L1 levels were characteristic of progressive disease (p = 0.01). In RRMS patients, CSF NFL, and CHI3L1 levels correlated with each other (r = 0.58), and with IgM-oligoclonal bands (p = 0.02 and p = 0.004, respectively). In addition, CSF CHI3L1 concentration was a predictor for 1-point EDSS worsening {HR = 2.99 [95% CI (1.27, 7.07)]} and progression during follow-up {HR = 18 [95% CI (2.31, 141.3)]}. The pattern of combined measure of biomarkers was useful to discriminate MS phenotypes and to anticipate clinical progression: RRMS more frequently presented high NFL combined with low CHI3L1 levels, compared to SPMS (HR 0.41 [0.18–0.82]), and PPMS (HR 0.46 [0.19–0.87]), while elevation of both biomarkers preceded diagnosis of clinical progression in RRMS patients (log rank = 0.02).Conclusions: Individual measures of CSF NFL and CHI3L1 are biomarkers of disease activity and progression, respectively. The pattern of combined measure discriminates MS phenotypes. It also predicts the subset of RRMS patients that will progress clinically allowing early intervention.

The main objective of our work is to describe the long-term results of myeloablative autologous hematopoietic stem cell transplant (AHSCT) in multiple sclerosis patients. Patients that failed to conventional therapies for multiple sclerosis (MS) underwent an approved protocol for AHSCT, which consisted of peripheral blood stem cell mobilization with cyclophosphamide and granulocyte colony-stimulating factor (G-CSF), followed by a conditioning regimen of BCNU, Etoposide, Ara-C, Melphalan IV, plus Rabbit Thymoglobulin. Thirty-eight MS patients have been transplanted since 1999. Thirty-one patients have been followed for more than 2 years (mean 8.4 years). There were 22 relapsing-remitting multiple sclerosis (RRMS) patients and 9 secondary progressive multiple sclerosis (SPMS) patients. No death related to AHSCT. A total of 10 patients (32.3%) had at least one relapse during post-AHSCT evolution, 6 patients in the RRMS group (27.2%) and 4 in the SPMS group (44.4%). After AHSCT, 7 patients (22.6%) experienced progression of disability, all within SP form. By contrast, no patients with RRMS experienced worsening of disability after a median follow-up of 5.4 years, 60% of them showed a sustained reduction in disability (SRD), defined as the improvement of 1.0 point in the expanded disability status scale (EDSS) sustains for 6 months (0.5 in cases of EDSS ≥ 5.5). The only clinical variable that predicted a poor response to AHSCT was a high EDSS in the year before transplant. AHSCT using the BEAM-ATG scheme is safe and efficacious to control the aggressive forms of RRMS.

Rituximab could be an effective and safe treatment in aggressive RRMS. Some selected PMS patients could also benefit from this treatment.

BackgroundDisease-modifying therapies are thought to reduce the conversion rate to secondary progressive multiple sclerosis.ObjectiveTo explore the rate, chronology, and contributing factors of conversion to the progressive phase in treated relapsing–remitting multiple sclerosis patients.MethodsOur study included 204 patients treated for relapsing–remitting multiple sclerosis between 1995 and 2002, prospectively followed to date. Kaplan–Meier analysis was applied to estimate the time until secondary progressive multiple sclerosis conversion, and multivariate survival analysis with a Cox regression model was used to analyse prognostic factors.ResultsRelapsing–remitting multiple sclerosis patients were continuously treated for 13 years (SD 4.5); 36.3% converted to secondary progressive multiple sclerosis at a mean age of 42.6 years (SD 10.6), a mean time of 8.2 years (SD 5.2) and an estimated mean time of 17.2 years (range 17.1–18.1). A multifocal relapse, age older than 34 years at disease onset and treatment failure independently predicted conversion to secondary progressive multiple sclerosis but did not influence the time to reach an Expanded Disability Status Scale of 6.0.ConclusionsThe favourable influence of disease-modifying therapies on long-term disability in relapsing–remitting multiple sclerosis is well established. However, the time to progression onset and the subsequent clinical course in treated patients seem similar to those previously reported in natural history studies. More studies are needed to clarify the effect of disease-modifying therapies once the progressive phase has been reached.

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