Mycobacterium avium subspecies paratuberculosis (MAP) infection, and its impact on gut microbiome of individuals with multiple sclerosis.

The microbial ecology of Mycobacterium avium subspecies paratuberculosis infections (MAP) within the context of Multiple Sclerosis (MS) is largely an unexplored topic in the literature. Thus, we have characterized the compositional and predicted functional differences of the gut microbiome between MS patients with MAP (MAP+) and without (MAP-) infection. This was done in the context of exposome differences (through self-reported filled questionnaires), principally in anthropometric and sociodemographic patterns to gain an understanding of the gut microbiome dynamics.

Network analysis of gut microbial communities reveal key genera for a multiple sclerosis cohort with Mycobacterium avium subspecies paratuberculosis infection.

Background: In gut ecosystems, there is a complex interplay of biotic and abiotic interactions that decide the overall fitness of an individual. Divulging the microbe-microbe and microbe-host interactions may lead to better strategies in disease management, as microbes rarely act in isolation. Network inference for microbial communities is often a challenging task limited by both analytical assumptions as well as experimental approaches.

Determinants of self-perceived quality of life in mildly disabled multiple sclerosis patients: a cross-sectional study.

Introduction: While the determinants influencing self-perceived health-related quality of life (spHRQoL) in persons with multiple sclerosis (pwMS) and severe physical impairment have been well investigated, their impact on pwMS with mild disability is poorly addressed. We aimed to investigate possible drivers of spHRQoL among Sardinian pwMS with an EDSS lower than 2.5.

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.

Antibody Response to HERV-K and HERV-W Envelope Epitopes in Patients with Myasthenia Gravis.

Myasthenia gravis is an antibody-mediated autoimmune neurological disorder characterized by impaired neuromuscular junction transmission, resulting in muscle weakness. Recently, the involvement of Human Endogenous Retroviruses (HERVs) in the pathophysiology of different immune-mediated and neurodegenerative diseases, such as multiple sclerosis, has been demonstrated. We aimed to investigate potential immune system involvement related to humoral responses targeting specific epitopes of HERV-K and HERV-W envelope proteins in myasthenia gravis.

RNA-binding proteins in autoimmunity: From genetics to molecular biology.

Autoimmune diseases (ADs) are chronic pathologies generated by the loss of immune tolerance to the body's own cells and tissues. There is growing recognition that RNA-binding proteins (RBPs) critically govern immunity in healthy and pathological conditions by modulating gene expression post-transcriptionally at all levels: nuclear mRNA splicing and modification, export to the cytoplasm, as well as cytoplasmic mRNA transport, storage, editing, stability, and translation. Despite enormous efforts to identify new therapies for ADs, definitive solutions are not yet available in many instances.

Antihuman Endogenous Retrovirus Immune Response and Adaptive Dysfunction in Autism.

ASD is a neurodevelopmental disorder of unknown aetiology but with a known contribution of pathogenic immune-mediated mechanisms. HERVs are associated with several neuropsychiatric diseases, including ASD. We studied anti-HERV-W, -K and -H-env immune profiles in ASD children to analyse differences between their respective mothers and child/mother control pairs and possible correlations to ASD severity and loss of adaptive abilities.

Rasagiline Withdrawal Syndrome in Parkinson's Disease.

Parkinson's disease (PD) patients using dopamine agonists can develop withdrawal symptoms, referred to as dopamine agonist withdrawal syndrome (DAWS), under dose tapering or discontinuation of these drugs. DAWS includes a severe stereotypical cluster of psychiatric and psychological symptoms encompassing severe mood and anxiety disturbances, autonomic symptoms, as well as generalized pain and drug cravings. However, symptoms of withdrawal of dopamine replacement therapies (DRT) are not simply limited to dopamine agonists tapering, as observed in PD patients on deep brain stimulation after dopaminergic drugs withdrawal related to surgery.

Effect of Different Disease-Modifying Therapies on Humoral Response to BNT162b2 Vaccine in Sardinian Multiple Sclerosis Patients.

Objectives: Vaccination against COVID-19 is highly recommended to patients affected by multiple sclerosis (MS); however, the impact of MS disease-modifying therapies (DMTs) on the immune response following vaccination has been only partially investigated. Here, we aimed to elucidate the effect of DMTs on the humoral immune response to mRNA-based anti-SARS-CoV-2 vaccines in MS patients.

Methods: We obtained sera from 912 Sardinian MS patients and 63 healthy controls 30 days after the second dose of BNT162b2 vaccine and tested them for SARS-CoV-2 response using anti-Spike (S) protein-based serology.

TDP-43 and HERV-K Envelope-Specific Immunogenic Epitopes Are Recognized in ALS Patients.

The human endogenous retrovirus-K (HERV-K) and TAR DNA-binding protein 43 (TDP-43) have been associated with the pathophysiology of amyotrophic lateral sclerosis (ALS). Given these findings, we investigated the humoral response against HERV-K envelope surface (env-su) glycoprotein antigens and TDP-43 in the plasma of ALS patients and healthy controls (HCs). The measured levels of Abs against the different epitopes' fragments were significantly elevated in ALS patients, both in long-survivor (LS) and newly diagnosed (ND) patients, compared to HCs.

HERV-K Modulates the Immune Response in ALS Patients.

Human endogenous retrovirus (HERV)-K env-su glycoprotein has been documented in amyotrophic lateral sclerosis (ALS), where HERV-K env-su antibody levels significantly correlated with clinical measures of disease severity. Herein, we investigated further the humoral and cell-mediated immune response against specific antigenic peptides derived from HERV-K in ALS. HERV-K env glycoprotein expression on peripheral blood mononuclear cells (PBMCs) membrane and cytokines and chemokines after stimulation with HERV-K env and HERV-K env were quantified in patients and healthy controls (HCs).

Maternal multiple sclerosis is not a risk factor for neurodevelopmental disorders in offspring.

Background: Childhood neurodevelopmental disorders (NDDs), including specific learning disorders (SLD), attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), are pathogenically linked to familial autoimmunity and maternal immune-mediated diseases during pregnancy.

Objective: We studied maternal MS as a potential risk factor for NDDs occurrence in offspring.

Methods: MS and control mothers were subjected to questionnaires to ascertain NDD diagnosis in their progeny and the occurrence of both autoimmune and neurodevelopment disorders in their families.

Long-term trajectory of acquired demyelinating syndrome and multiple sclerosis in children.

Aim: We assessed the frequency, characteristics, and future trajectory of monophasic acquired demyelinating syndromes (ADS) associated with conversion to paediatric multiple sclerosis.

Method: This was a retrospective observational study of Sardinian children (<18y of age) with onset of ADS between 2001 and 2018.

Results: We identified 44 children with ADS (21 males, 23 females; median age at onset 16y, range 4mo-18y), 21 of whom were already presenting with criteria for paediatric multiple sclerosis.

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.

Antibody response against HERV-W in patients with MOG-IgG associated disorders, multiple sclerosis and NMOSD.

Increased expression of the retroviruses of HERV-W family has been linked to multiple sclerosis (MS) pathophysiology; nothing is known at the moment about MOG-IgG associated disorders. We compared antibody response against HERV-W peptides among patients with MOG-IgG associated disorders, multiple sclerosis (MS) and aquaporin-4 (AQP4)-IgG positive neuromyelitis optica spectrum disorder (NMOSD). A total of 102 serum samples were retrospectively analyzed.

Inflammation, Infectious Triggers, and Parkinson's Disease.

Parkinson's disease is a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons of the substantia nigra pars compacta with a reduction of dopamine concentration in the striatum. The complex interaction between genetic and environmental factors seems to play a role in determining susceptibility to PD and may explain the heterogeneity observed in clinical presentations. The exact etiology is not yet clear, but different possible causes have been identified.

Determinants of therapy switch in multiple sclerosis treatment-naïve patients: A real-life study.

Background: With many options now available, first therapy choice is challenging in multiple sclerosis (MS) and depends mainly on neurologist and patient preferences.

Objectives: To identify prognostic factors for early switch after first therapy choice.

Methods: Newly diagnosed relapsing-remitting MS patients from 24 Italian centers were included.

Assessing association of comorbidities with treatment choice and persistence in MS: A real-life multicenter study.

Objective: To assess whether the presence of concomitant diseases at multiple sclerosis (MS) diagnosis is associated with the choice and the treatment persistence in an Italian MS cohort.

Methods: We included newly diagnosed patients (2010-2016) followed in 20 MS centers and collected demographic and clinical data. We evaluated baseline factors related to the presence of comorbidities and the association between comorbidities and the clinical course of MS and the time to the first treatment switch.

An innovative training program based on virtual reality and treadmill: effects on gait of persons with multiple sclerosis.

Aim: In this single blind randomized controlled trial, we examined the effect of a virtual reality-based training on gait of people with multiple sclerosis.

Methods: Twenty-five individuals with multiple sclerosis with mild to moderate disability were randomly assigned to either the control group (n = 11) or the experimental group (n = 14). The subjects in the control group received treadmill training.

Effect of Contralateral Strength Training on Muscle Weakness in People With Multiple Sclerosis: Proof-of-Concept Case Series.

Background: The contralateral strength training (CST) effect is a transfer of muscle performance to the untrained limb following training of the contralateral side.

Objective: The aim of this study was to explore, in individuals with multiple sclerosis (MS) presenting marked lower limb strength asymmetry, the effectiveness of CST on management of muscle weakness of the more-affected limb following training of the less-affected limb.

Design: A single-subject research design was used.

Personality traits predict perceived health-related quality of life in persons with multiple sclerosis.

Background: Personality traits can affect health-related quality of life (HRQoL) in different disorders. In multiple sclerosis (MS), personality traits can determine patients' willingness to take on more risky treatment options, predispose to neuropsychiatric symptoms and affect coping strategies.

Objectives: We investigated the role of personality traits as possible predictors of HRQoL in a large cohort of persons with MS (PwMS).