Interleukin-10 contrasts inflammatory synaptopathy and central neurodegenerative damage in multiple sclerosis.

Proinflammatory cytokines are implicated in promoting neurodegeneration in multiple sclerosis (MS) by affecting excitatory and inhibitory transmission at central synapses. Conversely, the synaptic effects of anti-inflammatory molecules remain underexplored, despite their potential neuroprotective properties and their presence in the cerebrospinal fluid (CSF) of patients. In a study involving 184 newly diagnosed relapsing-remitting (RR)-MS patients, we investigated whether CSF levels of the anti-inflammatory interleukin (IL)-10 were linked to disease severity and neurodegeneration measures.

NEDA-3 achievement in early highly active relapsing remitting multiple sclerosis patients treated with Ocrelizumab or Natalizumab.

Background: in the early stages of Multiple Sclerosis (MS), initiating high-efficacy disease-modifying therapy (HE DMTs) may represent an optimal strategy for delaying neurological damage and long-term disease progression, especially in highly active MS patients (HAMS). Natalizumab (NAT) and Ocrelizumab (OCR) are recognized as HE DMTs with significant anti-inflammatory effects. This study investigates NEDA-3 achievement in treatment-naïve HAMS patients receiving NAT or OCR over three years.

Ocrelizumab and ofatumumab comparison: an Italian real-world propensity score matched study.

Background: The management of Multiple Sclerosis (MS) has undergone transformative evolution with the introduction of high-efficacy disease-modifying therapies (DMTs), specifically anti-CD20 monoclonal antibodies, such as ocrelizumab (OCR) and ofatumumab (OFA).

Materials And Methods: This is an independent retrospective cohort study in Relapsing MS (RMS) patients followed at eight Italian MS centers who initiated treatment with OCR or OFA in the participating centers and with at least 12 months on therapy. A generalized linear regression model inverse probability of treatment weight (IPTW) PS-adjusted was performed to evaluate the relationship between annualized relapse rate (ARR) and treatment groups.

Treatment modifiers across different regimens of natalizumab treatment in MS: An Italian real-world experience.

Despite its widespread use in clinical practice, the effectiveness of natalizumab extended interval dosing (EID) adopted from treatment start across different treatment intervals and individual modifiers (body mass index - BMI) is still under-investigated. Here, seven-hundred and forty-five multiple sclerosis (MS) patients, exposed to natalizumab for 3.30 ​± ​1.

The role of ethnicity and native-country income in multiple sclerosis: the Italian multicentre study (MS-MigIT).

Objective: Multiple sclerosis (MS) is a complex disorder in which environmental and genetic factors interact modifying disease risk and course. This multicentre, case-control study involving 18 Italian MS Centres investigated MS course by ethnicity and native-country economic status in foreign-born patients living in Italy.

Methods: We identified 457 MS patients who migrated to Italy and 893 age- and sex-matched native-born Italian patients.

Ofatumumab and Early Immunological Cells Subset Characterization in Naïve Relapsing Multiple Sclerosis Patients: A Real-World Study.

Background: Ofatumumab (OFA) is a fully human anti-CD20 monoclonal antibody administered with a 20 mg subcutaneous monthly dosing regimen.

Methods: Inclusion criteria were patients: 1) aged 18-55; 2) with a confirmed diagnosis of relapsing Multiple Sclerosis (RMS), per the revised 2010 McDonald criteria; 2) who started OFA according to Italian Medicines Agency prescription rules and within 12 months from the RMS diagnosis; 3) naïve to any disease-modifying therapy. The primary outcome was to offer an overview of cellular subsets of RMS naïve patients (time 0) and then after 4 weeks (time 1) and 12 weeks (time 2) on therapy with OFA in a real-world setting.

Symptomatic COVID-19 course and outcomes after three mRNA vaccine doses in multiple sclerosis patients treated with high-efficacy DMTs.

Background: Little is known about COVID-19 course and outcomes after a third booster dose of mRNA vaccine against SARS-CoV-2 (mRNA-Vax) in patients with multiple sclerosis (pwMS) treated with ocrelizumab (OCR) and fingolimod (FNG), which showed a weakened immune response to mRNA-vax.

Objectives: The aim of this study was to evaluate COVID-19 course and outcomes in pwMS on OCR and FNG after receiving the third dose of mRNA-Vax and to compare it with pwMS on natalizumab (NTZ).

Methods: Inclusion criteria: >18 years of age, being treated with OCR/FNG/NTZ since the first mRNA-Vax dose; COVID-19 after a third booster dose of mRNA-Vax; no steroids use.

Frailty and relapse activity in multiple sclerosis: A longitudinal observation.

Recent cross-sectional investigations suggest a relationship between frailty, as measured by Frailty Index (FI), and multiple sclerosis (MS). However, if and how frailty is associated with relapse activity in MS is still unknown. To explore this issue, a one-year follow-up study involving 471 patients was conducted.

Patients with multiple sclerosis choose a collaborative role in making treatment decision: results from the Italian multicenter SWITCH study.

Background: Clinicians are increasingly recognizing the importance of shared decision-making in complex treatment choices, highlighting the importance of the patient's rationale and motivation for switching therapies. This study aimed to evaluate the association between different modalities of changing multiple sclerosis (MS) treatments, cognitive profile and attitude and preferences of patients concerning treatment choice.

Methods: This multicenter cross-sectional study was conducted at 28 Italian MS centers in the period between June 2016 and June 2017.

Preventive exercise attenuates IL-2-driven mood disorders in multiple sclerosis.

Background: Elevated levels of specific proinflammatory molecules in the cerebrospinal fluid (CSF) have been associated with disability progression, enhanced neurodegeneration and higher incidence of mood disorders in people with multiple sclerosis (MS). Studies in animal models of MS suggest that preventive exercise may play an immunomodulatory activity, with beneficial effects on both motor deficits and behavioral alterations. Here we explored the impact of lifestyle physical activity on clinical presentation and associated central inflammation in a large group of newly diagnosed patients with MS.

Usability of an application device for nabiximols oromucosal spray in patients with upper limb impaired multiple sclerosis.

This study aimed to assess the usability of a specific EU-available application device for Sativex (US adopted name: nabiximols) cannabinoid-based oromucosal spray in patients with multiple sclerosis (MS) and spasticity-related upper limb and hand impairment in routine daily practice. MS patients with upper limb and hand impairment evaluated the usability of the device using an 18-item questionnaire. 60 patients were included.

Predictors of Cladribine Effectiveness and Safety in Multiple Sclerosis: A Real-World, Multicenter, 2-Year Follow-Up Study.

Introduction: Cladribine administration has been approved for the treatment of relapsing-remitting multiple sclerosis (MS) in 2017; thus, data on cladribine in a real-world setting are still emerging.

Methods: We report on cladribine effectiveness, safety profile, and treatment response predictors in 243 patients with MS followed at eight tertiary MS centers. Study outcomes were: (1) No Evidence of Disease Activity-3 (NEDA-3) status and its components (absence of clinical relapses, MRI activity, and sustained disability worsening); (2) development of grade III/IV lymphopenia.

Influence of Previous Disease-Modifying Drug Exposure on T-Lymphocyte Dynamic in Patients With Multiple Sclerosis Treated With Ocrelizumab.

Background And Objectives: To investigate the longitudinal dynamic of lymphocyte subsets during treatment with ocrelizumab (OCR) in patients with multiple sclerosis (PwMS).

Methods: A multicenter retrospective study was conducted in 161 PwMS starting treatment with OCR grouped in naive (naive, n = 40), switching from fingolimod (FTY, n = 52), and switching from other immunomodulating drugs (other, n = 69). Mean lymphocyte subset (total, CD3, CD4, CD8, CD20, and natural killer) counts were analyzed at baseline, 6 months, and 12 months.

Safety of Natalizumab infusion in multiple sclerosis patients during active SARS-CoV-2 infection.

COVID-19 pandemic represented a challenge in the management of treatments for Multiple Sclerosis (MS), such as Natalizumab (NTZ). NTZ interferes with the homing of lymphocytes into the central nervous system, reducing immune surveillance against opportunistic infection. Although NTZ efficacy starts to decline 8 weeks after the last infusion, increasing the risk of disease reactivation, evidence is lacking on the safety of reinfusion during active SARS-CoV-2 infection.

Age at Disease Onset Associates With Oxidative Stress, Neuroinflammation, and Impaired Synaptic Plasticity in Relapsing-Remitting Multiple Sclerosis.

Age at onset is the main risk factor for disease progression in patients with relapsing-remitting multiple sclerosis (RR-MS). In this cross-sectional study, we explored whether older age is associated with specific disease features involved in the progression independent of relapse activity (PIRA). In 266 patients with RR-MS, the associations between age at onset, clinical characteristics, cerebrospinal fluid (CSF) levels of lactate, and that of several inflammatory molecules were analyzed.

Cerebrospinal fluid levels of L-glutamate signal central inflammatory neurodegeneration in multiple sclerosis.

Excessive extracellular concentrations of L-glutamate (L-Glu) can be neurotoxic and contribute to neurodegenerative processes in multiple sclerosis (MS). The association between cerebrospinal fluid (CSF) L-Glu levels, clinical features, and inflammatory biomarkers in patients with MS remains unclear. In 179 MS patients (relapsing remitting, RR, N = 157; secondary progressive/primary progressive, SP/PP, N = 22), CSF levels of L-Glu at diagnosis were determined and compared with those obtained in a group of 40 patients with non-inflammatory/non-degenerative disorders.

Disease Reactivation after Fingolimod Discontinuation in Pregnant Multiple Sclerosis Patients.

Recent studies estimated an incidence of 4-25% of disease rebound after withdrawal of fingolimod (FTY) for any reason, but specific data on disease reactivation after FTY withdrawal due to pregnancy are limited. The aim of the study was to evaluate the frequency and predictors of disease reactivation in patients who stopped FTY for pregnancy. A multicentre retrospective cohort study was conducted in four Italian MS centres in 2013-2019.

COVID-19 vaccines in multiple sclerosis treated with cladribine or ocrelizumab.

Since the recent approval of vaccines against COVID-19, efficacy concerns emerged for MS patients treated with immunosuppressive drugs. We report our experience in four patients, under cladribine (two) or under ocrelizumab (two) treatment, all with low lymphocyte count, three of them vaccinated after 3 months from the last dose with good immune response, one (under ocrelizumab) after 2 months, without developing an appropriate title of antibodies. This experience suggests that the discriminant for the response to the vaccine is not the lymphocyte count but the timing of the vaccination.