Regional hippocampal atrophy reflects memory impairment in patients with early relapsing remitting multiple sclerosis.

Background: Research work has shown that hippocampal subfields are atrophic to varying extents in multiple sclerosis (MS) patients. However, studies examining the functional implications of subfield-specific hippocampal damage in early MS are limited. We aim to gain insights into the relationship between hippocampal atrophy and memory function by investigating the correlation between global and regional hippocampal atrophy and memory performance in early MS patients.

Quality of care provided by Multiple Sclerosis Centers during Covid-19 pandemic: Results of an Italian multicenter patient-centered survey.

Background: Covid-19 pandemic impacted on management of people with Multiple Sclerosis (pwMS). Level of satisfaction of pwMS regarding the care received by the staff of Multiple Sclerosis Centers (MSCs) during the pandemic was not fully investigated. In a large patient-centered multicenter study, the therapeutic adherence and quality of care of MSCs was assessed.

Antibody response elicited by the SARS-CoV-2 vaccine booster in patients with multiple sclerosis: Who gains from it?

Background And Purpose: Although two doses of COVID-19 vaccine elicited a protective humoral response in most persons with multiple sclerosis (pwMS), a significant group of them treated with immunosuppressive disease-modifying therapies (DMTs) showed less efficient responses.

Methods: This prospective multicenter observational study evaluates differences in immune response after a third vaccine dose in pwMS.

Results: Four hundred seventy-three pwMS were analyzed.

Breakthrough SARS-CoV-2 infections in MS patients on disease-modifying therapies.

Background: Patients with multiple sclerosis (pwMS) treated with anti-CD20 or fingolimod showed a reduced humoral response to SARS-CoV-2 vaccines.

Objective: In this study we aimed to monitor the risk of breakthrough SARS-CoV-2 infection in pwMS on different disease-modifying therapies (DMTs).

Methods: Data on the number of vaccinated patients and the number of patients with a breakthrough infection were retrospectively collected in 27 Italian MS centers.

Breakthrough SARS-CoV-2 infections after COVID-19 mRNA vaccination in MS patients on disease modifying therapies during the Delta and the Omicron waves in Italy.

Background: In this study we aimed to monitor the risk of breakthrough SARS-CoV-2 infection in patients with MS (pwMS) under different DMTs and to identify correlates of reduced protection.

Methods: This is a prospective Italian multicenter cohort study, long-term clinical follow-up of the CovaXiMS (Covid-19 vaccine in Multiple Sclerosis) study. 1855 pwMS scheduled for SARS-CoV-2 mRNA vaccination were enrolled and followed up to a mean time of 10 months.

Effect of BDNF Val66Met polymorphism on hippocampal subfields in multiple sclerosis patients.

Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism was shown to strongly affect BDNF function, but its role in modulating gray matter damage in multiple sclerosis (MS) patients is still not clear. Given BDNF relevance on the hippocampus, we aimed to explore BDNF Val66Met polymorphism effect on hippocampal subfield volumes and its role in cognitive functioning in MS patients. Using a 3T scanner, we obtained dual-echo and 3DT1-weighted sequences from 50 MS patients and 15 healthy controls (HC) consecutively enrolled.

Effect of SARS-CoV-2 mRNA vaccination in MS patients treated with disease modifying therapies.

Background: In patients with Multiple Sclerosis (pwMS) disease-modifying therapies (DMTs) affects immune response to antigens. Therefore, post-vaccination serological assessments are needed to evaluate the effect of the vaccine on SARS-CoV-2 antibody response.

Methods: We designed a prospective multicenter cohort study enrolling pwMS who were scheduled for SARS-Cov-2 vaccination with mRNA vaccines (BNT162b2, Pfizer/BioNTech,Inc or mRNA-1273, Moderna Tx,Inc).

Mild gray matter atrophy in patients with long-standing multiple sclerosis and favorable clinical course.

The mechanisms responsible for the favorable clinical course in multiple sclerosis (MS) remain unclear. In this longitudinal study, we assessed whether magnetic resonance imaging (MRI)-based changes in focal and diffuse brain damage are associated with a long-term favorable MS diseases course. We found that global brain and gray matter (GM) atrophy changes were milder in MS patients with long-standing disease (⩾30 years from onset) and favorable (no/minimal disability) clinical course than in sex-age-matched disable MS patients, independently of lesions accumulation.

Dynamics of pseudo-atrophy in RRMS reveals predominant gray matter compartmentalization.

Objective: To assess the dynamics of "pseudo-atrophy," the accelerated brain volume loss observed after initiation of anti-inflammatory therapies, in patients with multiple sclerosis (MS).

Methods: Monthly magnetic resonance imaging (MRI) data of patients from the IMPROVE clinical study (NCT00441103) comparing relapsing-remitting MS patients treated with interferon beta-1a (IFNβ-1a) for 40 weeks versus those receiving placebo (16 weeks) and then IFNβ-1a (24 weeks) were used to assess percentage of gray (PGMVC) and white matter (PWMVC) volume changes. Comparisons of PGMVC and PWMVC slopes were performed with a mixed effect linear model.

Mapping the Progressive Treatment-Related Reduction of Active MRI Lesions in Multiple Sclerosis.

To assess treatment-related spatio-temporal dynamics of active MRI lesions in relapsing-remitting multiple sclerosis (RRMS) patients. We performed a analysis of MRI data acquired at weeks 4, 8, 12, and 16, in RRMS patients from the multicenter randomized IMPROVE study, which compares patients treated with 44 mcg subcutaneous interferon β-1a three times weekly ( = 120) versus placebo ( = 60). We created lesion probability maps (LPMs) of the cumulative combined unique active (CUA) lesions in each patient group at each time point.

Cladribine vs other drugs in MS: Merging randomized trial with real-life data.

Objective: Cladribine tablets were tested against placebo in randomized controlled trials (RCTs). In this study, the effectiveness of cladribine vs other approved drugs in patients with relapsing-remitting MS (RRMS) was compared by matching RCT to observational data.

Methods: Data from the pivotal trial assessing cladribine tablets vs placebo (CLARITY) were propensity score matched to data from the Italian multicenter database i-MuST.

Longitudinal Assessment of Multiple Sclerosis with the Brain-Age Paradigm.

Objective: During the natural course of multiple sclerosis (MS), the brain is exposed to aging as well as disease effects. Brain aging can be modeled statistically; the so-called "brain-age" paradigm. Here, we evaluated whether brain-predicted age difference (brain-PAD) was sensitive to the presence of MS, clinical progression, and future outcomes.

Gray matter atrophy cannot be fully explained by white matter damage in patients with MS.

Background: Source-based morphometry (SBM) was recently used for non-random "patterns" of gray matter (GM) atrophy or white matter (WM) microstructural damage.

Objective: To assess whether and to what extent such patterns may be inter-related in MS.

Methods: SBM was applied to images of GM concentration and fractional anisotropy (FA) in MS patients ( = 41, median EDSS = 1) and normal controls (NC,  = 28).

The dilemma of benign multiple sclerosis: Can we predict the risk of losing the "benign status"? A 12-year follow-up study.

Background: Definition of benign multiple sclerosis (BMS) remains controversial. Moreover, a sizeable proportion of classically defined BMS patients may be no longer benign (NLB) when re-assessed in the long-term. In a previous work, we found that after a five-year follow-up, a clinical score was able to identify patients at risk of losing their benign status.

Pronounced Structural and Functional Damage in Early Adult Pediatric-Onset Multiple Sclerosis with No or Minimal Clinical Disability.

Pediatric-onset multiple sclerosis (POMS) may represent a model of vulnerability to damage occurring during a period of active maturation of the human brain. Whereas adaptive mechanisms seem to take place in the POMS brain in the short-medium term, natural history studies have shown that these patients reach irreversible disability, despite slower progression, at a significantly younger age than adult-onset MS (AOMS) patients. We tested for the first time whether significant brain alterations already occurred in POMS patients in their early adulthood and with no or minimal disability ( = 15) in comparison with age- and disability-matched AOMS patients ( = 14) and to normal controls (NC,  = 20).

Vitamin D levels in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

Besides its well known function on bone metabolism, vitamin D role in cerebrovascular pathologies including cerebral small vessel disease has been confirmed by recent meta-analysis. In this study, we measured vitamin D levels in 56 Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) patients (mean age 49.9) with no or minimal disability (modified Ranking Score, mRS ≤2) and in 56 age, sex and seasonality matched healthy controls.

Assessing response to interferon-β in a multicenter dataset of patients with MS.

Objective: To provide new insights into the role of markers of response to interferon-β therapy in multiple sclerosis (MS) in a multicenter setting, focusing on the relevance of MRI lesions in combination with clinical variables.

Methods: A large multicenter clinical dataset was collected within the Magnetic Resonance Imaging in MS (MAGNIMS) network. This included a large cohort of patients with relapsing-remitting MS on interferon-β treatment, MRI and clinical assessments during the first year of treatment, and clinical follow-up of at least 2 additional years.

Mitochondrial dysfunction in hereditary spastic paraparesis with mutations in DDHD1/SPG28.

Mutations in DDHD1 cause the SPG28 subtype of hereditary spastic paraplegia (HSP). Recent studies suggested that mitochondrial dysfunction occurs in SPG28. Here we describe two siblings with SPG28, and report evidence of mitochondrial impairment in skeletal muscle and skin fibroblasts.

Structural MRI correlates of cognitive impairment in patients with multiple sclerosis: A Multicenter Study.

In a multicenter setting, we applied voxel-based methods to different structural MR imaging modalities to define the relative contributions of focal lesions, normal-appearing white matter (NAWM), and gray matter (GM) damage and their regional distribution to cognitive deficits as well as impairment of specific cognitive domains in multiple sclerosis (MS) patients. Approval of the institutional review boards was obtained, together with written informed consent from all participants. Standardized neuropsychological assessment and conventional, diffusion tensor and volumetric brain MRI sequences were collected from 61 relapsing-remitting MS patients and 61 healthy controls (HC) from seven centers.

Establishing pathological cut-offs of brain atrophy rates in multiple sclerosis.

Objective: To assess whether it is feasible to establish specific cut-off values able to discriminate 'physiological' or 'pathological' brain volume rates in patients with multiple sclerosis (MS).

Methods: The study was based on the analysis of longitudinal MRI data sets of patients with MS (n=206, 87% relapsing-remitting, 7% secondary progressive and 6% primary progressive) and healthy controls (HC; n=35). Brain atrophy rates were computed over a mean follow-up of 7.