Long-term modifications of the peripheral immune repertoire after switching from sequestering disease-modifying treatments in multiple sclerosis.

Background: Scarce data are available on the long-term immunological effects of multiple sclerosis (MS) disease-modifying treatments (DMTs).

Objectives: This study aimed to investigate the long-term modifications of the peripheral immune repertoire on interruption of a sequestering DMT (natalizumab, fingolimod) and switch to another high-efficacy DMT.

Methods: Lymphocyte subpopulations were assessed, every 6 months up to 48 months, in patients switched from fingolimod or natalizumab to ocrelizumab, and in patients switched from fingolimod to natalizumab, compared to patients switched to ocrelizumab or natalizumab from a moderate-efficacy DMT and to naive patients.

Ocrelizumab in MS patients with persistence of disease activity after alemtuzumab: A multi-center Italian study.

Background: The reason why some multiple sclerosis (MS) patients show disease activity after alemtuzumab (ALM) is still unclear, but ocrelizumab (OCR) could represent an interesting sequential therapeutic approach.

Objectives: To investigate safety and efficacy of OCR in MS patients with disease activity after two ALM courses.

Methods: Observational retrospective multi-centers Italian cohort study.

Determinants and Biomarkers of Progression Independent of Relapses in Multiple Sclerosis.

Clinical, pathological, and imaging evidence in multiple sclerosis (MS) suggests that a smoldering inflammatory activity is present from the earliest stages of the disease and underlies the progression of disability, which proceeds relentlessly and independently of clinical and radiological relapses (PIRA). The complex system of pathological events driving "chronic" worsening is likely linked with the early accumulation of compartmentalized inflammation within the central nervous system as well as insufficient repair phenomena and mitochondrial failure. These mechanisms are partially lesion-independent and differ from those causing clinical relapses and the formation of new focal demyelinating lesions; they lead to neuroaxonal dysfunction and death, myelin loss, glia alterations, and finally, a neuronal network dysfunction outweighing central nervous system (CNS) compensatory mechanisms.

Identifying definite patterns of unmet needs in patients with multiple sclerosis using unsupervised machine learning.

Introduction: People with multiple sclerosis (PwMS) exhibit a spectrum of needs that extend beyond solely disease-related determinants. Investigating unmet needs from the patient perspective may address daily difficulties and optimize care. Our aim was to identify patterns of unmet needs among PwMS and their determinants.

Association of MRI leptomeningeal enhancement with disability worsening in progressive multiple sclerosis: A clinical and post-mortem study.

Background: Leptomeningeal enhancement (LME) has been described as a biomarker of meningeal inflammation in multiple sclerosis (MS).

Objective: The aim of this study was to (1) assess if LME is predictive of disability worsening in progressive MS (pMS) patients and (2) investigate the pathological substrates of LME in an independent post-mortem MS series.

Methods: In total, 115 pMS patients were imaged yearly with 1.

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.

SARS-CoV-2 pandemic as a model to assess the relationship between intercurrent viral infections and disease activity in Multiple Sclerosis: A propensity score matched case-control study.

Introduction: An association between intercurrent viral respiratory infections and exacerbations of Multiple Sclerosis (MS) disease activity has been proposed by several studies. Considering the rapid spread of SARS-CoV2 worldwide and the systematic effort to immediately detect all incident cases with specific diagnostic tests, the pandemic can represent an interesting experimental model to assess the relationship between viral respiratory infections and MS disease activity.

Aims And Methods: In this study, we have performed a propensity score matched case-control study with a prospective clinical/MRI follow-up, on a cohort of relapsing-remitting MS (RRMS) patients who tested positive for SARS-CoV2 in the period 2020-2022, with the aim to evaluate if the SARS-CoV2 infection influences the short-term risk of disease activity.

Previous disease-modifying treatments influence T lymphocyte kinetics in people with multiple sclerosis switching to ocrelizumab.

Background: Recently, concern has been raised about the influence of the previous disease-modifying treatments (DMTs) on the clinical efficacy of ocrelizumab (OCR). We aimed to evaluate whether the previous DMT affects the lymphocyte subset kinetics in people with Multiple Sclerosis (MS) switching to OCR.

Methods: This is a multicenter, retrospective, real-world study on consecutive MS patients who started or switched to OCR.

Association of vitamin D serum levels and vitamin D supplementation with B cell kinetics and disease activity in Multiple Sclerosis patients treated with ocrelizumab: an Italian multi-center study.

Background: Several observational studies have shown an association between low circulating levels of 25-hydroxy- vitamin D (25(OH)D) and an increase in inflammatory activity in Multiple Sclerosis (MS). Among its immunomodulatory functions, 25(OH)D suppresses proliferation and immunoglobulin production of B cells. 25(OH)D supplementation has been associated with better radiological outcomes in MS patients treated with interferon (IFN)-B, glatiramer acetate, fingolimod, natalizumab and rituximab.

Fetal and post-natal growth in infants of mothers with multiple sclerosis: A case-control stud.

Background: Multiple sclerosis does not seem to adversely affect fetal and neonatal outcomes, although some studies reported a possible reduction in mean birth weight and length, and a higher incidence of preterm delivery, mainly in relation to the exposure to disease-modifying drugs (DMDs) during pregnancy. Few data are available on intrauterine fetal growth and postnatal somatic development of newborns from mothers with multiple sclerosis compared to those from healthy women. For these reasons, we decided to investigate fetal growth, neonatal anthropometric parameters, and postnatal somatic development up to 12 months of life in offsprings from MS mothers.

Dietary habits, nutritional status and risk of a first demyelinating event: an incident case-control study in a southern European cohort.

Background: The relationship between dietary habits and multiple sclerosis (MS) risk is still controversial. Most studies have involved populations from Scandinavia, North America, and Australia. Data on populations from southern Europe (an area of high MS prevalence) are scarce.

Impact of COVID-19 lockdown on progressive multiple sclerosis patients.

Introduction: The COVID-19 pandemic caused major changes in the lifestyle and in the access to health services worldwide. Progressive multiple sclerosis (pMS) patients are a vulnerable population at high risk of disability worsening.

Objective And Methods: The objective of this study was to assess the health outcomes of COVID-19 lockdown in a cohort of 225 pMS patients.

Case Report: Covid-19 in Multiple Sclerosis Patients Treated With Ocrelizumab: A Case Series.

Limited data are available on the course of Coronavirus disease 2019 (COVID-19) in people with Multiple Sclerosis (MS). More real-world data are needed to help the MS community to manage MS treatment properly. In particular, it is important to understand the impact of immunosuppressive therapies used to treat MS on the outcome of COVID-19.

CD19 Cell Count at Baseline Predicts B Cell Repopulation at 6 and 12 Months in Multiple Sclerosis Patients Treated with Ocrelizumab.

Background: The kinetics of B cell repopulation in MS patients treated with Ocrelizumab is highly variable, suggesting that a fixed dosage and time scheduling might be not optimal. We aimed to investigate whether B cell repopulation kinetics influences clinical and radiological outcomes and whether circulating immune asset at baseline affects B cell repopulation kinetics.

Methods: 218 MS patients treated with Ocrelizumab were included.

Acute and chronic synaptic pathology in multiple sclerosis gray matter.

Objectives: To investigate the extent of synaptic loss, and the contribution of gray matter (GM) inflammation and demyelination to synaptic loss, in multiple sclerosis (MS) brain tissue.

Methods: This study was performed on two different post-mortem series of MS and control brains, including deep GM and cortical GM. MS brain samples had been specifically selected for the presence of active demyelinating GM lesions.

Paraneoplastic neuromyelitis optica spectrum disorders: a case series.

Aquaporin-4 antibody (AQP4-IgG) neuromyelitis optica spectrum disorders (NMOSD) are rare idiopathic autoimmune diseases, presenting with optic neuritis (ON), longitudinally extensive transverse myelitis (LETM), and brainstem syndromes and a prevalence range between 0.5 and 4/100,000. Only 3% to 25% of NMOSD have been described as a paraneoplastic (PN) syndrome (PNNMOSD).

Inhibition of Human Neutrophil Functions In Vitro by Multiple Sclerosis Disease-Modifying Therapies.

There is a growing optimism about the potential of new disease-modifying therapies (DMTs) in the management of relapsing-remitting multiple sclerosis (RRMS) patients. However, this initial enthusiasm has been tempered by evidence indicating that multiple sclerosis (MS) patients undergoing DMT may be at higher risk of developing infections through incompletely understood mechanisms. As neutrophils provide the first line of defense against pathogens, here we have compared the effects of some of the commonly used MS DMTs (i.

Assessing balance in non-disabled subjects with multiple sclerosis: Validation of the Fullerton Advanced Balance Scale.

Objective: To validate the Fullerton Advanced Balance (FAB) scale for high-functioning non-disabled people with multiple sclerosis (PwMS).

Design: Cross-sectional study.

Participants: A convenience sample of early-diagnosed PwMS (N = 82; Expanded Disability Status Scale score ≤ 2.

Overexpression of sphingosine-1-phosphate receptors on reactive astrocytes drives neuropathology of multiple sclerosis rebound after fingolimod discontinuation.

We present the neuropathological description of an autoptic case of fatal rebound of disease activity after fingolimod discontinuation in a multiple sclerosis patient. MRI prior to the fatal outcome showed several large tumefactive demyelinating lesions. These lesions were characterized by prominent astrocytic gliosis, with a remarkable preponderance of large hypertrophic reactive astrocytes showing intense expression of sphingosine-1-phosphate receptor 1.

Thrombopoietin/TGF-β1 Loop Regulates Megakaryocyte Extracellular Matrix Component Synthesis.

Extracellular matrix (ECM) components initiate crucial biochemical and biomechanical cues that are required for bone marrow homeostasis. In our research, we prove that a peri-cellular matrix composed primarily of type III and type IV collagens, and fibronectin surrounds human megakaryocytes in the bone marrow. The data we collected support the hypothesis that bone marrow megakaryocytes possess a complete mechanism to synthesize the ECM components, and that thrombopoietin is a pivotal regulator of this new function inducing transforming growth factor-β1 (TGF-β1) release and consequent activation of the downstream pathways, both in vitro and in vivo.

Nanostructured TiO₂ Surfaces Promote Human Bone Marrow Mesenchymal Stem Cells Differentiation to Osteoblasts.

Micro- and nano-patterning/modification are emerging strategies to improve surfaces properties that may influence critically cells adherence and differentiation. Aim of this work was to study the in vitro biological reactivity of human bone marrow mesenchymal stem cells (hBMSCs) to a nanostructured titanium dioxide (TiO₂) surface in comparison to a coverglass (Glass) in two different culture conditions: with (osteogenic medium (OM)) and without (proliferative medium (PM)) osteogenic factors. To evaluate cell adhesion, hBMSCs phosphorylated focal adhesion kinase (pFAK) foci were analyzed by confocal laser scanning microscopy (CLSM) at 24 h: the TiO₂ surface showed a higher number of pFAK foci with respect to Glass.

Progranulin genetic polymorphisms influence progression of disability and relapse recovery in multiple sclerosis.

Background: Progranulin (GRN) is a multifunctional protein involved in inflammation and repair, and also a neurotrophic factor critical for neuronal survival. Progranulin is strongly expressed in multiple sclerosis (MS) brains by macrophages and microglia.

Methods: In this study we evaluated GRN genetic variability in 400 MS patients, in correlation with clinical variables such as disease severity and relapse recovery.