1,25(OH)D3 Differently Modulates the Secretory Activity of IFN-DC and IL4-DC: A Study in Cells from Healthy Donors and MS Patients.

Immune mechanisms play an essential role in driving multiple sclerosis (MS) and altered trafficking and/or activation of dendritic cells (DC) were observed in the central nervous system and cerebrospinal fluid of MS patients. Interferon β (IFNβ) has been used as a first-line therapy in MS for almost three decades and vitamin D deficiency is a recognized environmental risk factor for MS. Both IFNβ and vitamin D modulate DC functions.

Changes in John Cunningham Virus Index in Multiple Sclerosis Patients Treated with Different Disease-Modifying Therapies.

Background: Progressive Multifocal Leukoencephalopathy (PML) is an opportunistic infection caused by John Cunningham virus (JCV) reactivation, potentially associated with natalizumab (NTZ) treatment for Multiple Sclerosis (MS). The anti-JCV antibodies titre (JCV index) increases during NTZ treatment; however, the effects of other disease-modifying therapies (DMTs) on the JCV index have not been fully explored.

Objective: The aim of the study was to evaluate changes in the JCV index during treatment with several DMTs.

Disease-modifying drugs can reduce disability progression in relapsing multiple sclerosis.

An ever-expanding number of disease-modifying drugs for multiple sclerosis have become available in recent years, after demonstrating efficacy in clinical trials. In the real-world setting, however, disease-modifying drugs are prescribed in patient populations that differ from those included in pivotal studies, where extreme age patients are usually excluded or under-represented. In this multicentre, observational, retrospective Italian cohort study, we evaluated treatment exposure in three cohorts of patients with relapsing-remitting multiple sclerosis defined by age at onset: paediatric-onset (≤18 years), adult-onset (18-49 years) and late-onset multiple sclerosis (≥50 years).

Early diagnosis of secondary progressive multiple sclerosis: focus on fluid and neurophysiological biomarkers.

Background And Aims: Most patients with multiple sclerosis presenting with a relapsing-remitting disease course at diagnosis transition to secondary progressive multiple sclerosis (SPMS) 1-2 decades after onset. SPMS is characterized by predominant neurodegeneration and atrophy. These pathogenic hallmarks result in unsatisfactory treatment response in SPMS patients.

Changes in Anti-JCV Antibody Status in a Large Population of Multiple Sclerosis Patients Treated with Natalizumab.

Introduction: Natalizumab (NTZ) can be associated with an opportunistic infection, progressive multifocal leukoencephalopathy (PML), caused by John Cunningham virus (JCV). High titer of anti-JCV antibody (JCV index) in patients treated with NTZ for over 2 years limit it use, leading to treatment discontinuation.

Objective: Aim of the study was to investigate the JCV index changes pre, during and post NTZ treatment and describe the trend after a long period of NTZ discontinuation.

Exit strategies for "needle fatigue" in multiple sclerosis: a propensity score-matched comparison study.

Patients with multiple sclerosis on long-term injectable therapies may suffer from the so-called "needle fatigue", i.e., a waning commitment to continue with the prescribed injectable treatment.

Secukinumab may be a valid treatment option in patients with CNS demyelination and concurrent ankylosing spondylitis: Report of two clinical cases.

The therapeutic approach to CNS demyelination associated to ankylosing spondylitis is a complex issue due to the contraindication of TNF inhibitors in demyelinating diseases. Secukinumab, a human IgG1κ monoclonal antibody that binds and inhibits IL-17A, was recently approved for the treatment of ankylosing spondylitis. We report the clinical cases of two patients affected by a CNS demyelinating disease and ankylosing spondylitis who were successfully treated with secukinumab, providing additional evidence of the feasibility of this therapeutic option when the use of TNF inhibitors is discouraged by challenging comorbidities.

Deep grey matter involvement and altered sensory gating in multiple sclerosis.

Background: Somatosensory temporal discrimination threshold (STDT) is altered in multiple sclerosis (MS). In healthy subjects (HS), voluntary movement modulates the STDT through mechanisms of subcortical sensory gating.

Objective: With neurophysiological and magnetic resonance imaging (MRI) techniques, we investigated sensory gating and sensorimotor integration in MS.

Photophobia in multiple sclerosis.

Background: Photophobia has never been investigated in MS.

Methods: In this pilot study we used photosensitivity questionnaire assessment (PAQ) to evaluate tolerability to light in 73 MS patients and 62 healthy controls.

Results: We identified a lower PAQ score and a higher number of photophobic subjects in MS than in controls.

Safety and Efficacy of Dimethyl Fumarate in Multiple Sclerosis: An Italian, Multicenter, Real-World Study.

Background: Two phase III trials have demonstrated the clinical and radiological efficacy of delayed-release dimethyl fumarate (DMF) in relapsing-remitting multiple sclerosis (RRMS). However, data on its safety and effectiveness in real-world practice are still limited.

Objectives: The aim of our study was to explore the safety and tolerability profile of DMF in RRMS.

Abortion induces reactivation of inflammation in relapsing-remitting multiple sclerosis.

Objective: To investigate clinical and radiological outcomes of women with relapsing-remitting multiple sclerosis (RRMS) undergoing abortion.

Methods: An independent, multicentre retrospective study was conducted collecting data from eight Italian MS centres. We compared the preconception and postabortion annualised relapse rate (ARR) and number of Gadolinium enhancing (Gd+) lesions, by analyses of covariance.

Fingolimod vs dimethyl fumarate in multiple sclerosis: A real-world propensity score-matched study.

Objective: To directly compare fingolimod (FNG) and dimethyl fumarate (DMF) on no evident disease activity (NEDA) status in patients with relapsing-remitting multiple sclerosis (RRMS) from 7 multiple sclerosis outpatient clinics in Central Italy.

Methods: We analyzed data of patients with RRMS who started an oral agent, namely DMF or FNG, either as first treatment (naives) or after switching from self-injectable drugs (switchers). We performed a propensity score (PS)-based nearest-neighbor matching within a caliper of 0.

The Prevalence of Multiple Sclerosis in the Metropolitan Area of Rome: A Capture-Recapture Analysis.

Background: Limited data are available on the prevalence of multiple sclerosis (MS) in central Italy. The objective of this study is to estimate MS prevalence in the metropolitan area of Rome.

Methods: We used the capture-recapture method to calculate prevalence estimates in the study area.

Prognostic indicators in pediatric clinically isolated syndrome.

Objective: To assess prognostic factors for a second clinical attack and a first disability-worsening event in pediatric clinically isolated syndrome (pCIS) suggestive of multiple sclerosis (MS) patients.

Methods: A cohort of 770 pCIS patients was followed up for at least 10 years. Cox proportional hazard models and Recursive Partitioning and Amalgamation (RECPAM) tree-regression were used to analyze data.

Real-world effectiveness of natalizumab and fingolimod compared with self-injectable drugs in non-responders and in treatment-naïve patients with multiple sclerosis.

In this independent, multicentre post-marketing study we directly compared the effectiveness of natalizumab (NTZ), fingolimod (FNG) and self-injectable drugs (INJ), in non-responders to first immunomodulating treatment and in highly active treatment-naïve patients with multiple sclerosis. As main outcome measure we considered the proportions of patients with no evidence of disease activity (NEDA-3), defined as absence of relapses, disability worsening and radiological activity. A total of 567 non-responders to interferon beta (IFNB) or glatiramer acetate (GA) [dataset A] and 216 highly active treatment-naïves [dataset B] were followed up to 24 months from the beginning of NTZ, FNG or INJ, i.

Natalizumab Affects T-Cell Phenotype in Multiple Sclerosis: Implications for JCV Reactivation.

The anti-CD49d monoclonal antibody natalizumab is currently an effective therapy against the relapsing-remitting form of multiple sclerosis (RRMS). Natalizumab therapeutic efficacy is limited by the reactivation of the John Cunningham polyomavirus (JCV) and development of progressive multifocal leukoencephalopathy (PML). To correlate natalizumab-induced phenotypic modifications of peripheral blood T-lymphocytes with JCV reactivation, JCV-specific antibodies (serum), JCV-DNA (blood and urine), CD49d expression and relative abundance of peripheral blood T-lymphocyte subsets were longitudinally assessed in 26 natalizumab-treated RRMS patients.

The Use of Immunosuppressant Therapy for Multiple Sclerosis in Italy: A Multicenter Retroprospective Study.

Introduction: Immunosuppressive agents (ISA) have been used in multiple sclerosis (MS) for decades, frequently as off label licensed therapies. Given the new MS treatment landscape, what place do ISA have in combating MS?

Methods: We conducted a retrospective multicentre study to investigate the frequency of ISA prescription in 17 Italian MS centres, and to describe the clinical factors related to ISA use.

Results: Out of 6,447 MS patients, 2,034 (31.

A dual concurrent mechanism explains trigeminal neuralgia in patients with multiple sclerosis.

Objective: In this clinical and neuroimaging study, we sought information on the possible role of neurovascular compression in multiple sclerosis (MS)-related trigeminal neuralgia (TN).

Methods: After screening 1,628 consecutive patients with MS, we enrolled 28 patients with definite unilateral MS-related TN. In these patients, we acquired dedicated 3T MRI scans, identified pontine demyelinating plaques, and, using highly specific diagnostic criteria, distinguished possible neurovascular compression.

Fingolimod versus interferon beta/glatiramer acetate after natalizumab suspension in multiple sclerosis.

The comparative effectiveness of fingolimod versus interferon beta/glatiramer acetate was assessed in a multicentre, observational, prospectively acquired cohort study including 613 patients with relapsing multiple sclerosis discontinuing natalizumab in the Italian iMedWeb registry. First, after natalizumab suspension, the relapse risk during the untreated wash-out period and during the course of switch therapies was estimated through Poisson regression analyses in separated models. During the wash-out period an increased risk of relapses was found in patients with a higher number of relapses before natalizumab treatment (incidence rate ratio = 1.

Intradetrusorial Botulinum Toxin in Patients with Multiple Sclerosis: A Neurophysiological Study.

Patients with multiple sclerosis (MS) often complain of urinary disturbances characterized by overactive bladder syndrome and difficulties in bladder emptying. The aim of the study was to investigate the pathophysiology of bladder dysfunction and the neurophysiological effects of intradetrusorial incobotulinum toxin A (BoNT/A) in patients with MS having both brain and spinal MS-related lesions. Twenty-five MS patients with neurogenic detrusor overactivity (NDO) underwent clinical evaluation and soleus Hoffmann reflex (H reflex) study during urodynamics.

OnabotulinumtoxinA intradetrusorial injections improve sexual function in female patients affected by multiple sclerosis: preliminary results.

Purpose: To investigate the effects of onabotulinum toxin type A (Onabot/A) intravesical injections on urinary and sexual function in a group of patients affected by multiple sclerosis (MS).

Methods: We enrolled 31 MS female patients with symptoms of overactive bladder and detrusor overactivity. All patients underwent urodynamics and were administered 3-day voiding diary, Incontinence Quality of Life (I-QoL) questionnaire, Female Sexual Function Index (FSFI) questionnaire, Hamilton Anxiety Rating Scale (HAM-A) and Hamilton Depression Rating Scale (HAM-D) before and 3 months after Onabot/A intravesical injection.

Increased circulating levels of vitamin D binding protein in MS patients.

Vitamin D (vitD) low status is currently considered a main environmental factor in multiple sclerosis (MS) etiology and pathogenesis. VitD and its metabolites are highly hydrophobic and circulate mostly bound to the vitamin D binding protein (DBP) and with lower affinity to albumin, while less than 1% are in a free form. The aim of this study was to investigate whether the circulating levels of either of the two vitD plasma carriers and/or their relationship are altered in MS.

CCL2 induction by 1,25(OH)2D3 in dendritic cells from healthy donors and multiple sclerosis patients.

CCL2 plays a pivotal role in the recruitment of different immune cells to sites of inflammation and evidence indicates its involvement in multiple sclerosis (MS) pathogenesis. MS lesions are characterized by an inflammatory infiltrate, whose nature is controlled by chemokines and cytokines, and elevated expression of CCL2 has been found in acute and chronic MS plaques within the brain. Vitamin D deficiency is currently considered one of the main environmental MS risk factors.

Opposite regulatory effects of IFN-β and IL-3 on C-type lectin receptors, antigen uptake, and phagocytosis in human macrophages.

CLRs are predominantly expressed in macrophages and myeloid DCs, where they play a key role in antigen recognition, scavenging, and host defense against pathogens. To identify novel immunoregulatory cytokines and networks involved in the control of these functions, we analyzed the coordinate effects of IFN-β and IL-3 on CLR expression, antigen uptake, and phagocytosis in human MDMs and MDDCs. We report that these cytokines exert opposite regulatory effects on the expression of CLRs and endocytic/phagocytic activities of MDMs.