Background And Objectives: Multiple sclerosis (MS) is common in adults while myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is rare. Our previous machine-learning algorithm, using clinical variables, ≤6 brain lesions, and no Dawson fingers, achieved 79% accuracy, 78% sensitivity, and 80% specificity in distinguishing MOGAD from MS but lacked validation. The aim of this study was to (1) evaluate the clinical/MRI algorithm for distinguishing MS from MOGAD, (2) develop a deep learning (DL) model, (3) assess the benefit of combining both, and (4) identify key differentiators using probability attention maps (PAMs).
View Article and Find Full Text PDFMult Scler
September 2025
Aging is associated with profound changes in cellular function (senescence) and affects various tissues and systems, including the immune system (immunosenescence). Despite the increasing average age of individuals with multiple sclerosis (MS), little is known about what happens to the immune system of aging people with MS or about the impact of immunomodulatory and immunosuppressive treatments for MS on the aging immune system. In this topical review, we discuss the concepts of physiological cellular senescence and immunosenescence, and we review the latest available data on immunosenescence in MS.
View Article and Find Full Text PDFMult Scler Relat Disord
August 2025
Background: Induction therapies for multiple sclerosis (MS), such as cladribine (CLAD), require multiple cycles to achieve full clinical effects, and the extent of immunosuppression from a single course is unclear. Fingolimod (FINGO), administered daily, provides a rapid anti-inflammatory effect, desirable for active MS.
Objectives: to compare the efficacy of the first course of CLAD versus FINGO over 12 months by analyzing clinical data, brain atrophy, retinal thinning, and diffusion MRI metrics of myelin and neuroaxonal integrity in the corpus callosum.
Objective: To establish recommendations based on an expert consensus on the early and appropriate use of high-efficacy disease-modifying therapies (HE-DMTs) in the management of multiple sclerosis (MS) patients, based on current clinical evidence and real-world practice in Italy.
Material And Methods: A Delphi panel comprising 65 neurologists from 54 Italian MS centers engaged in a two-round consensus process. Experts rated 43 statements across five domains: therapeutic goals, definitions of HE-DMT, MS patient profiling, and use of HE-DMT at diagnosis and later in MS course, using a 5-point Likert scale.
We aimed to explore whether Anti-Müllerian hormone (AMH) levels are associated with disease activity in multiple sclerosis (MS) women. AMH levels were similar between 73 patients and 146 controls. Analyses adjusted for age showed higher AMH levels in patients who relapsed within the last 12 months (yes: 4.
View Article and Find Full Text PDFIEEE Trans Neural Syst Rehabil Eng
July 2025
Gait analysis plays a crucial role in assessing mobility impairments and monitoring disease progression in individuals with Multiple Sclerosis (MS). Markerless, video-based methods offer a non-invasive, practical alternative to traditional marker-based systems, making them particularly suitable for clinical applications. This study employs a markerless video-based approach to extract spatio-temporal and kinematic parameters from 25 individuals with MS and 25 age- and sex-matched unimpaired controls.
View Article and Find Full Text PDFBackground And Objectives: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system. Its etiology may involve both genetic and environmental factors, including vitamin D levels, body mass index, infections, and smoking. This is the first comprehensive systematic review with meta-analysis that synthesizes and explore the role of many environmental risk factors in the etiology of MS.
View Article and Find Full Text PDFMultiple sclerosis (MS) presents a spectrum of disease activities, making prognostication and treatment challenging. Our focus on aggressive MS (AMS), a subset lacking a universally accepted definition, aims to clarify its identification and management. Here we critically dissect the different criteria for defining AMS based on the latest research and consensus, the early prognostic factors which can unambiguously identify aggressive variants early in the disease course and the available high-efficacy therapies, with a special focus on autologous haematopoietic stem cell transplantation (AHSCT), which is considered a standard of care for relapsing-remitting MS refractory to disease-modifying treatments.
View Article and Find Full Text PDFObjective: To evaluate the long-term impact of early intensive treatment (EIT) versus escalation (ESC) strategies using high-efficacy disease-modifying therapies (HE-DMTs) on disability progression in relapsing multiple sclerosis (RMS).
Methods: This observational study included 4878 RMS patients from the Italian Multiple Sclerosis Register. Eligible participants initiated their first disease-modifying therapy (DMT) within 3 years of disease onset and had ≥ 5 years of follow-up with at least three Expanded Disability Status Scale (EDSS) evaluations.
Objectives: To assess the impact of age on the superiority of highly effective (HE) disease-modifying treatments (DMTs) compared to platform DMTs in a real-world population of relapsing MS patients (pwMS).
Methods: A total of 20,984 pwMS were extracted from the Italian Multiple Sclerosis Register with a diagnosis of Clinically Isolated Syndrome or Relapsing-Remitting MS, at least four Expanded Disability Status Scale (EDSS) evaluations and 2 years follow-up, starting DMT. The baseline was the nearest visit to the first DMT starting date.
IEEE Trans Neural Syst Rehabil Eng
June 2025
Multiple Sclerosis negatively affects hand function in 60% of cases. Upper extremity dysfunction in persons with Multiple Sclerosis (PwMS) has previously been linked to slower, more variable movement, increased visual response delays (Tv), and neuroimaging evidence of altered brain activity; yet no one knows how these aspects relate to each other. This work combines clinical, kinematic, sensorimotor control, and neural imaging techniques to gain a more complete understanding of how upper extremity dysfunction arises in PwMS.
View Article and Find Full Text PDFIntroduction: Safety concerns have been raised regarding fingolimod to siponimod transition in people with Secondary Progressive Multiple Sclerosis (SPMS).
Objective: To explore factors associated with the choice of switching from fingolimod to siponimod and the safety of this sequencing.
Methods: We conducted a prospective observational study that included patients who had a confirmed diagnosis of SPMS at the time of study entry and had been treated with fingolimod for at least two years.
BackgroundCognitive rehabilitation and exercise training are promising approaches for improving cognition in persons with progressive multiple sclerosis (MS). Identifying heterogeneity of change and factors that influence the effects of cognitive rehabilitation and/or exercise training on cognitive outcomes at the individual level have direct relevance for developing tailored and optimized rehabilitation interventions for improving cognition in progressive MS.ObjectiveThis study involved a secondary data analysis from the CogEx trial in progressive MS.
View Article and Find Full Text PDFBackground: Cerebrospinal fluid (CSF) oligoclonal IgM bands (OCMBs) have been suggested as prognostic biomarkers in MS, but serum OCMBs meaning is still uncertain.
Objectives: We aimed to assess frequency and clinical relevance of all OCMB patterns.
Methods: In this retrospective cohort study, 136 paired sera-CSF from consecutive persons with MS (pwMS) were tested in 2 centers for OCMBs using isoelectric focusing-immunoblotting.
Background: The cerebellum is a functionally and anatomically complex structure, which, in multiple sclerosis (MS), is affected by focal white/gray matter lesions and by secondary neurodegeneration of afferent/efferent connections to the supratentorial brain and the spinal cord.
Objectives: To assess the efficacy of ocrelizumab compared with interferon β-1a (IFN β-1a)/placebo on cerebellar volume loss and the effect of switching to ocrelizumab on volume change in the Phase III trials in relapsing MS (RMS, OPERA I/II) and in primary progressive MS (PPMS, ORATORIO).
Methods: Cerebellar volume change was computed using paired Jacobian integration and analyzed using a mixed-effect repeated measurement model.
Multiple sclerosis (MS) is a chronic central nervous system disease characterized by neurodegeneration and inflammation. Neurofilament light chain (NfL), a protein released during axonal injury, has gained recognition as a potential biomarker for monitoring MS progression and treatment response. Evidence indicates that blood NfL (bNfL) offers a minimally invasive, cost-effective tool for tracking neuroaxonal damage.
View Article and Find Full Text PDFBackground: Multiple Sclerosis (MS) is the first cause of non-traumatic neurological disability in young adults. Primary and secondary progressive MS are still lacking effective treatments. A new nutraceutical product made of lyophilised leaves of bioengineered kiwi plants (Actinidia deliciosa) overexpressing osmotin has recently been developed.
View Article and Find Full Text PDFBackground: Physical activity (PA) has been recommended in multiple sclerosis (MS) to maintain good physical fitness and mental health, reduce the severity of symptoms and risk of relapse, and improve quality of life. Pilates has been suggested as an ideal PA to manage physical, cognitive, and psychological symptoms of MS and a useful method to maintain and improve balance and gait.
Objective: This paper presents the protocol for a study that aims to evaluate the efficacy on the physical domain (specifically balance and gait) of a home-based, self-managed PA intervention delivered through the MS-FIT exergame (HELAGLOBE Società a responsabilità limitata).
The classification of multiple sclerosis (MS) into the two distinct phases of relapsing-remitting and progressive, including primary progressive and secondary progressive phenotypes (PPMS and SPMS, respectively) has long been accepted; however, there are several unmet needs associated with this particular model. The observation that both inflammation and neurodegeneration are present from the onset of MS has resulted in a paradigm shift towards MS as a disease continuum driven by pathological mechanisms underlying clinical progression. Here we report the results from a meeting of Italian MS specialists, exploring the evolving perception of MS pathobiology and its implications for diagnosis and treatment.
View Article and Find Full Text PDFBackground: High-efficacy disease-modifying therapies (HETs) have substantially improved multiple sclerosis (MS) management, yet ongoing cognitive decline remains a concern. This study aims to assess Symbol Digit Modalities Test (SDMT) changes in patients with stable relapsing-remitting MS (RRMS) treated with HETs and to evaluate the role of baseline MRI biomarkers as predictors of SDMT changes.
Methods: Consecutive patients with RRMS treated with HETs underwent clinical, SDMT and MRI assessment at baseline with SDMT and clinical re-evaluation after 24 months.
Ann Clin Transl Neurol
March 2025
Objectives: We aim to investigate cognitive phenotype distribution and MRI correlates across pediatric-, elderly-, and adult-onset MS patients as a function of disease duration.
Methods: In this cross-sectional study, we enrolled 1262 MS patients and 238 healthy controls, with neurological and cognitive assessments. A subset of 222 MS patients and 92 controls underwent 3T-MRI scan for brain atrophy and lesion analysis.
Mult Scler Relat Disord
February 2025
Background: A recent application of the GRADE guidelines indicated Faremus, a 5-day neuromodulation for 15 min per day via transcranial direct current stimulation (tDCS), as medium to highly recommendable for alleviating fatigue in multiple sclerosis (MS).
Methods: With this pilot study we aimed to evaluate the feasibility, acceptance, safety, and effectiveness of the Faremus treatment carried out in a multicenter context. The Rome unit prepared the intervention, supplied the personalized electrodes to the San Martino Hospital in Genova, where the neurological team enrolled the population of fatigued people with multiple sclerosis (PwMS) and carried out the treatment.
Objective: To investigate, in two cohorts including patients with multiple sclerosis (MS) and migraine, (i) the prevalence of the "central vein sign" (CVS), (ii) the spatial distribution of positive CVS (CVS+) lesions, (iii) the threshold of CVS+ lesions able to distinguish MS from migraine with high sensitivity and specificity.
Methods: A total of 70 patients with MS/clinically isolated syndrome and 50 age- and sex-matched patients with migraine underwent a 3-T magnetic resonance imaging scan. The CVS was evaluated according to current guidelines, excluding eight patients with migraine who did not show white matter (WM) lesions.
Nat Rev Neurol
March 2025
Autologous haematopoietic stem cell transplantation (AHSCT) is a treatment option for relapsing forms of multiple sclerosis (MS) that are refractory to disease-modifying therapy (DMT). AHSCT after failure of high-efficacy DMT in aggressive forms of relapsing-remitting MS is a generally accepted indication, yet the optimal placement of this approach in the treatment sequence is not universally agreed upon. Uncertainties also remain with respect to other indications, such as in rapidly evolving, severe, treatment-naive MS, progressive MS, and neuromyelitis optica spectrum disorder (NMOSD).
View Article and Find Full Text PDFTher Adv Neurol Disord
January 2025
Background: Characterizing Cladribine tablets prescription pattern in daily clinical practice is crucial for optimizing multiple sclerosis (MS) treatment.
Objectives: To describe efficacy, safety profile and new disease-modifying therapy (DMT) prescriptions following Cladribine treatment.
Design: Independent retrospective cohort study in patients followed at six Italian MS centres.