Long-Term Treatment With Ocrelizumab in Patients With Early-Stage Relapsing MS: Nine-Year Data From the OPERA Studies Open-Label Extension.

Background And Objectives: Patients with multiple sclerosis (MS) may demonstrate better disease control when treatment is initiated on high-efficacy disease-modifying therapies (DMTs) from onset. This subgroup analysis assessed the long-term efficacy and safety profile of the high-efficacy DMT ocrelizumab (OCR) as first-line therapy for early-stage relapsing MS (RMS).

Methods: Post hoc exploratory analyses of efficacy and safety were performed in a subgroup of treatment-naive patients with RMS who received ≥1 dose of OCR in the multicenter OPERA I/II (NCT01247324/NCT01412333) studies.

Three-year treatment with anti-CGRP monoclonal antibodies modifies migraine course: the prospective, multicenter I-GRAINE study.

Objectives: To determine whether extending anti-CGRP mAb treatment beyond 3 years influences migraine course, we analyzed migraine frequency during the first month of treatment discontinuation following three 12-month treatment cycles (Ts).

Methods: This multicenter, prospective, real-world study enrolled 212 patients with high-frequency episodic migraine (HFEM) or chronic migraine (CM) who completed three consecutive Ts of subcutaneous anti-CGRP mAbs. Discontinuation periods (D1, D2, D3) were defined as the first month after T1, T2, and T3, respectively.

Pediatric, adult, and late onset multiple sclerosis: Cognitive phenotypes and gray matter atrophy.

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.

Favorable long-term cognitive outcomes following recurrent ARIA linked to amyloid-lowering therapies: two cases.

Introduction: The large-scale approval of anti-amyloid monoclonal antibodies for treating Alzheimer's disease (AD) has raised concerns about their safety due to treatment-emergent amyloid-related imaging abnormalities (ARIA).

Methods: We present two cases of patients diagnosed with mild cognitive impairment due to AD who were enrolled in the GRADUATE I clinical trial. They received subcutaneous gantenerumab every two weeks during the study period.

Longitudinal assessment of white matter alterations in progressive supranuclear palsy variants using diffusion tractography.

Introduction: White matter (WM) tract degeneration is a characteristic feature of progressive supranuclear palsy (PSP), with longitudinal changes observed in PSP-Richardson's syndrome (PSP-RS). Little, however, is known about the other PSP variants. We assessed cross-sectional and longitudinal WM degeneration across PSP variants using diffusion tractography.

Subventricular Zone Microstructure in Pediatric-Onset Multiple Sclerosis.

Objective: The aim of this study was to explore the microstructural dynamics of the subventricular zone (SVZ) with aging and their associations with clinical disability and brain structural damage in pediatric-onset multiple sclerosis (MS) patients.

Methods: One-hundred and forty-one pediatric-onset MS patients (67 pediatric and 74 adults with pediatric-onset) and 233 healthy controls (HC) underwent neurological and 3.0 T MRI assessment.

Conformational Antibodies to Proteolipid Protein-1 and Its Peripheral Isoform DM20 in Patients With CNS Autoimmune Demyelinating Disorders.

Background And Objectives: Antibodies to proteolipid protein-1 (PLP1-IgG), a major central myelin protein also expressed in the peripheral nervous system (PNS) as the isoform DM20, have been previously identified mostly in patients with multiple sclerosis (MS), with unclear clinical implications. However, most studies relied on nonconformational immunoassays and included few patients with non-MS CNS autoimmune demyelinating disorders (ADDs). We aimed to investigate conformational PLP1-IgG in the whole ADD spectrum.

Ocrelizumab dose selection for treatment of pediatric relapsing-remitting multiple sclerosis: results of the OPERETTA I study.

Background: The presented study identified the appropriate ocrelizumab dosing regimen for patients with pediatric-onset multiple sclerosis (POMS).

Methods: Patients with POMS aged 10-17 years were enrolled into cohort 1 (body weight [BW] < 40 kg, ocrelizumab 300 mg) and cohort 2 (BW ≥ 40 kg, ocrelizumab 600 mg) during a 24-week dose-exploration period (DEP), followed by an optional ocrelizumab (given every 24 weeks) extension period.

Primary Endpoints: pharmacokinetics, pharmacodynamics (CD19 B-cell count); secondary endpoint: safety; exploratory endpoints: MRI activity, protocol-defined relapses, Expanded Disability Status Scale (EDSS) score change.

Soma and neurite density abnormalities of paramagnetic rim lesions and core-sign lesions in multiple sclerosis.

Background: In multiple sclerosis (MS), susceptibility-weighted imaging (SWI) may reveal white matter lesions (WML) with a paramagnetic rim ("paramagnetic rim lesions" [PRLs]) or diffuse hypointensity ("core-sign lesions"), reflecting different stages of WML evolution.

Objective: Using the soma and neurite density imaging (SANDI) model on diffusion-weighted magnetic resonance imaging (MRI), we characterized microstructural abnormalities of MS PRLs and core-sign lesions and their clinical relevance.

Methods: Forty MS patients and 20 healthy controls (HC) underwent a 3 T brain MRI.

Family physicians' perspectives on outcomes, processes, and policies in dementia care.

The rapid rise in numbers of people living with Alzheimer's disease and related disorders (ADRD) poses major challenges to health systems and policy. Although primary care clinicians provide ongoing medical care for 80% of affected individuals, they face persistent barriers to providing high-quality dementia care. We conducted qualitative interviews with family physicians ( = 20) to understand what core outcomes they consider most important and what care processes and systems and policy strategies they propose to achieve them.

Implementing proximity care for people with multiple sclerosis in Italy: the bottom-up approach of the StayHome project.

Objective: In Italy, around 137,000 people live with multiple sclerosis, facing organizational complexities due to the current model's limited focus on proximity care. This project aims to define a proximity model, in accordance with recent developments in the Italian healthcare landscape, engaging over 150 healthcare stakeholders and potentially impacting approximately 14,000 patients.

Methods: An analysis was pursued to map the multiple sclerosis pathway, followed by interviews to capture the actual implementation in Italian Multiple Sclerosis Centers.

High-frequency epidural electrical stimulation reduces spasticity and facilitates walking recovery in patients with spinal cord injury.

Spinal cord injury (SCI) causes severe motor and sensory deficits, and there are currently no approved treatments for recovery. Nearly 70% of patients with SCI experience pathological muscle cocontraction and spasticity, accompanied by clinical signs such as patellar hyperreflexia and ankle clonus. The integration of epidural electrical stimulation (EES) of the spinal cord with rehabilitation has substantial potential to improve recovery of motor functions; however, abnormal muscle cocontraction and spasticity may limit the benefit of these interventions and hinder the effectiveness of EES in promoting functional movements.

CAR-T Cells for the Treatment of Central Nervous System Tumours: Known and Emerging Neurotoxicities.

The advent of chimeric antigen receptor (CAR)-T cells has recently changed the prognosis of relapsing/refractory diffuse large B-cell lymphomas, showing response rates as high as 60 to 80%. Common toxicities reported in the pivotal clinical trials include the cytokine release syndrome (CRS) and the Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS), a stereotyped encephalopathy related to myeloid cell activation and blood-brain barrier dysfunction, presenting with a distinctive cascade of dysgraphia, aphasia, disorientation, attention deficits, vigilance impairment, motor symptoms, seizures, and diffuse brain oedema. The tremendous oncological efficacy of CAR-T cells observed in systemic B-cell malignancies is leading to their growing use in patients with primary or secondary central nervous system (CNS) lymphomas and in patients with solid tumours, including several CNS cancers.

More Than the Sum of Its Parts: Disrupted Core Periphery of Multiplex Brain Networks in Multiple Sclerosis.

Disruptions to brain networks, measured using structural (sMRI), diffusion (dMRI), or functional (fMRI) MRI, have been shown in people with multiple sclerosis (PwMS), highlighting the relevance of regions in the core of the connectome but yielding mixed results depending on the studied connectivity domain. Using a multilayer network approach, we integrated these three modalities to portray an enriched representation of the brain's core-periphery organization and explore its alterations in PwMS. In this retrospective cross-sectional study, we selected PwMS and healthy controls with complete multimodal brain MRI acquisitions from 13 European centers within the MAGNIMS network.

Conservation of structural brain connectivity in people with multiple sclerosis.

Multiple sclerosis (MS) is a neurodegenerative disease that affects the central nervous system. Structures affected in MS include the corpus callosum, connecting the hemispheres. Studies have shown that in mammalian brains, structural connectivity is organized according to a conservation principle, an inverse relationship between intra- and interhemispheric connectivity.

Rhizobacteria and silicon modulate defense, oxidative stress, and suppress blast disease in upland rice plants in low phosphorus soils under field conditions.

Rhizobacteria and silicon fertilization synergism suppress leaf and panicle Blast, and mitigates biotic stress in rice plants. Association of bioagents and silicon is synergistic for mitigating leaf and panicle blast and low phosphorus (P) levels in upland rice, under greenhouse conditions. This study aimed to evaluate the potential of the bioagents and silicon interaction on blast disease severity suppression in upland rice plants, under field low P conditions.

Expanded and independent validation of the NoMoFA scale for Parkinson's disease: the Italian version.

Introduction: Non-motor symptoms (NMS) in Parkinson's disease (PD) can fluctuate daily, impacting patient quality of life. The Non-Motor Fluctuation Assessment (NoMoFA) Questionnaire, a recently validated tool, quantifies NMS fluctuations during ON- and OFF-medication states. Our study aimed to validate the Italian version of NoMoFA, comparing its results to the original validation and further exploring its clinimetric properties.

"I consider myself to be a leader": a qualitative exploration of early career women family physicians' intentions to assume a leadership role.

Background: Despite the increasing presence of women in US medical schools over the past 25 years, gender equity in medical leadership remains elusive. This qualitative study delves deeper into definitions of institutional leadership roles, who they are designed for, and how women currently contribute in unrecognized and uncompensated leadership positions.

Methods: We recruited family physicians who responded to the American Board of Family Medicine 2022 or 2023 graduate survey.

Association of the Cervical Canal Area With Disability and Progression in People With Multiple Sclerosis.

Background And Objectives: In multiple sclerosis (MS), brain reserve serves as a protective factor against cognitive impairment. Previous research has suggested a structural counterpart in the spine-spinal cord reserve-seemed to be associated with physical disability. This study aimed to investigate the potential of the cervical canal area (CCaA) as a proxy for spinal cord reserve in a multicentric cohort of people with MS (PwMS).

Unveiling preferences in multiple sclerosis care: insights from an Italian discrete-choice experiment with patients and healthcare professionals.

Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating, neurodegenerative disease of the central nervous system, significantly impacting patients' quality of life. Understanding patient and healthcare professional (HCP) preferences for MS treatments is crucial for optimizing therapeutic strategies and improving adherence and outcomes. This Discrete-Choice Experiment (DCE) assesses preferences for various MS treatment attributes among Italian patients and HCPs.

Heterogeneity of aerobic fitness changes with exercise training in progressive multiple sclerosis: Secondary, exploratory analysis of data from the CogEx trial.

Background: There is heterogeneity of aerobic fitness (VO) changes with a standardized exercise training stimulus in the general population (i.e. some participants demonstrate improvements, others no change, and some a reduction in VO).