De-escalating and discontinuing disease-modifying therapies in multiple sclerosis.

The development of disease-modifying therapies (DMTs) for the treatment of multiple sclerosis (MS) has been highly successful in recent decades. It is now widely accepted that early initiation of DMTs after disease onset is associated with a better long-term prognosis. However, the question of when and how to de-escalate or discontinue DMTs remains open and critical.

Association between paramagnetic rim lesions and pulvinar iron depletion in persons with multiple sclerosis.

Background: The deep gray matter (DGM), especially the pulvinar, and the white matter surrounding chronic active lesions have demonstrated depleted iron levels, indicating a possible mechanistic link. However, no studies have investigated the potential relationship between these phenomena.

Objectives: The study aimed to determine whether PRLs were associated with pulvinar iron depletion and, if so, whether this relationship was spatially mediated.

Neuroimaging markers and disability scales in multiple sclerosis: A systematic review and meta-analysis.

Background: Multiple sclerosis (MS) is a central nervous system disorder marked by progressive neurological impairments. Magnetic resonance imaging (MRI) parameters are key paraclinical measures that play a crucial role in the diagnosis, prognosis, and monitoring of MS-related disability. This study aims to analyze and summarize the existing literature on the correlation between MRI parameters and disability in people with MS (pwMS).

Determinants of long-term paramagnetic rim lesion evolution in people with multiple sclerosis.

Objective: Baseline paramagnetic rim lesion (PRL) load predicts disease progression in people with multiple sclerosis (pwMS). Understanding how PRLs relate to other known MS-related factors, and the practical utility of PRLs in clinical trials, is crucial for informing clinical decision-making and guiding development of novel disease-modifying treatments (DMTs).

Methods: This study included 152 pwMS enrolled in a larger prospective, longitudinal cohort study who had 3T MRI scans and clinical assessments at baseline and 5- or 10-year follow-ups.

Utility of icobrain for brain volumetry in multiple sclerosis clinical practice.

Background: Few studies on multiple sclerosis (MS) have explored the variability of percentage brain volume change (PBVC) measurements obtained from different clinical MRIs. In a retrospective multicentre cohort study, we quantified the variability of annualised PBVC in clinical MRIs.

Methods: Clinical MRIs of relapse-onset MS patients were assessed by icobrain.

Characteristics and predictors of disease course in children initially presenting with ADEM.

ADEM is an inflammatory disease, with new onset polyfocal neurologic symptoms, encephalopathy and multifocal demyelination, typically in childhood. Initial diagnosis of ADEM is challenging and up to 20 % of children with MS or NMOSD are initially diagnosed with ADEM. We describe characteristics of patients with monophasic ADEM vs.

Associations Between Paramagnetic Rim Lesion Evolution and Clinical and Radiologic Disease Progression in Persons With Multiple Sclerosis.

Background And Objectives: Recent technological advances have enabled visualizing in vivo a subset of chronic active brain lesions in persons with multiple sclerosis (pwMS), referred to as "paramagnetic rim lesions" (PRLs), with iron-sensitive MRI. PRLs predict future clinical disease progression, making them a promising clinical and translational imaging marker. However, it is unknown how disease progression is modified by PRL evolution (PRL disappearance, new PRL appearance).

Greater humoral EBV response may be associated with choroid plexus inflammation in progressive MS.

Choroid plexus (CP) inflammation can be quantified in vivo with MRI in people with multiple sclerosis (pwMS). It remains unknown whether Epstein Barr Virus (EBV) is related to CP changes. Total of 170 pwMS (116 relapsing-remitting; RRMS and 54 progressive MS; PMS) underwent MRI examination and measurement of humoral anti-EBV response.

Nuclear-Magnetic-Resonance-Spectroscopy-Derived Serum Biomarkers of Metabolic Vulnerability Are Associated with Disability and Neurodegeneration in Multiple Sclerosis.

Purpose: Metabolic vulnerabilities can exacerbate inflammatory injury and inhibit repair in multiple sclerosis (MS). The purpose was to evaluate whether blood biomarkers of inflammatory and metabolic vulnerability are associated with MS disability and neurodegeneration.

Methods: Proton nuclear magnetic resonance spectra were obtained from serum samples from 153 healthy controls, 187 relapsing-remitting, and 91 progressive MS patients.

Dyslipidemias in multiple sclerosis.

Purpose: To investigate the frequency of dyslipidemia phenotypes in multiple sclerosis and to assess the associations with lipoprotein particle size distributions.

Methods: This cross-sectional study included 203 healthy controls (HC), 221 relapsing-remitting MS (RRMS), and 126 progressive MS (PMS). A lipid profile with total cholesterol, high-density lipoprotein cholesterol (HDL-C), triglycerides, and apolipoprotein B levels were measured.

Cognitive progression independent of relapse in multiple sclerosis.

Background: Substantial physical-disability worsening in relapsing-remitting multiple sclerosis (RRMS) occurs outside of clinically recorded relapse. This phenomenon, termed progression independent of relapse activity (PIRA), is yet to be established for cognitive decline.

Methods: Retrospective analysis of RRMS patients.

Early Adversity and Socioeconomic Factors in Pediatric Multiple Sclerosis: A Case-Control Study.

Background And Objectives: Psychosocial adversity and stress, known to predispose adults to neurodegenerative and inflammatory immune disorders, are widespread among children who experience socioeconomic disadvantage, and the associated neurotoxicity and proinflammatory profile may predispose these children to multiple sclerosis (MS). We sought to determine associations of socioeconomic disadvantage and psychosocial adversity with odds of pediatric-onset MS (POMS), age at POMS onset, and POMS disease activity.

Methods: This case-control study used data collected across 17 sites in the United States by the Environmental and Genetic Risk Factors for Pediatric Multiple Sclerosis Study.

Increased intraindividual variability (IIV) in reaction time is the earliest indicator of cognitive change in MS: A two-year observational study.

Background: Cognitive decline in multiple sclerosis (MS) is common, but unpredictable, and increases with disease duration. As such, early detection of cognitive decline may improve the effectiveness of interventions. To that end, the Symbol Digit Modalities Test (SDMT) is effective in detecting slow processing speed as it relates to cognitive impairment, and intraindividual variability (IIV) observed in trials assessing continuous reaction time (RT) may be a useful indicator of early cognitive changes.

Comorbid onset of cardiovascular diagnosis and long-term confirmed disability progression in multiple sclerosis: A 15-year follow-up study.

Background: People with multiple sclerosis (pwMS) have greater prevalence of comorbid cardiovascular diseases (CVD) when compared to the general population despite similar frequency of CV risk factors.

Objective: Determine the impact of comorbid-onset of CVD diagnosis on long-term confirmed disability progression (CDP).

Methods: 276 pwMS (29 clinically isolated syndrome, 130 relapsing-remitting and 117 progressive) were clinically followed an average of 14.

Post-Partum Clinical and Patient-Reported Outcome Changes in Mothers with Multiple Sclerosis: Findings from the NAPPREMS Study.

: Pregnancy in mothers with multiple sclerosis (MS) commonly results in significant changes in disease activity and changes in clinical care, including the discontinuation of disease modifying therapy (DMT). This study aimed at understanding the clinical and patient-reported outcomes (PROs) before, during and 1-year after delivery. : A total of 30 pregnant mothers with MS were recruited as part of the study.

Serum Biomarker Signatures of Choroid Plexus Volume Changes in Multiple Sclerosis.

Increased choroid plexus (CP) volume has been recently implicated as a potential predictor of worse multiple sclerosis (MS) outcomes. The biomarker signature of CP changes in MS are currently unknown. To determine the blood-based biomarker characteristics of the cross-sectional and longitudinal MRI-based CP changes in a heterogeneous group of people with MS (pwMS), a total of 202 pwMS (148 pwRRMS and 54 pwPMS) underwent MRI examination at baseline and at a 5-year follow-up.

Clinical risk stratification: Development and validation of the DAAE score, a tool for estimating patient risk of transition to secondary progressive multiple sclerosis.

Background: Because secondary progressive multiple sclerosis (SPMS) is associated with worse prognosis, early predictive tools are needed. We aimed to use systematic literature review and advanced methods to create and validate a clinical tool for estimating individual patient risk of transition to SPMS over five years.

Methods: Data from the Jacobs Multiple Sclerosis Center (JMSC) and the Multiple Sclerosis Center Amsterdam (MSCA) was collected between 1994 and 2022.

Cognitive function in severe progressive multiple sclerosis.

Cognitive impairment is common in multiple sclerosis and negatively impacts quality of life. Cognitive status has yet to be described in people with severe progressive multiple sclerosis, in whom conventional neuropsychological testing is exceptionally difficult. The objective for the study was to characterize cognitive performance in severe progressive multiple sclerosis and compare them with age-, sex- and disease duration-matched less disabled people with multiple sclerosis using a specifically developed auditory, non-motor test of attention/cognitive processing speed-Auditory Test of Processing Speed.

Cognitive performance and magnetic resonance imaging in people with multiple sclerosis: A systematic review and meta-analysis.

Background: Several studies have shown the different relationships between cognitive functions and structural magnetic resonance imaging (MRI) measurements in people with multiple sclerosis (pwMS). However, there is an ongoing debate regarding the magnitude of correlation between MRI measurements and specific cognitive function tests. This systematic review and meta-analysis aimed to synthesize the most consistent correlations between MRI measurements and cognitive function in pwMS.

Lower arterial cerebral blood flow is associated with worse neuroinflammation and immunomodulation composite proteomic scores.

Background: Brain hypoperfusion is linked with worse physical, cognitive and MRI outcomes in multiple sclerosis (MS). Understanding the proteomic signatures related to hypoperfusion could provide insights into the pathophysiological mechanism.

Methods: 140 people with MS (pwMS; 86 clinically isolated syndrome (CIS)/relapsing-remitting (RRMS) and 54 progressive (PMS)) were included.

Effects of Physical Therapy and Dalfampridine on Function and Quality of Life in Nonambulatory Individuals With Multiple Sclerosis: A Randomized Controlled Trial.

Background: Decreases in mobility, quality of life (QOL) and cognition are commonly seen in people with multiple sclerosis (MS). Physical therapy (PT) and exercise have been shown to improve many symptoms in ambulatory individuals with MS; however, evidence in nonambulatory people with MS is lacking. Dalfampridine is a US Food and Drug Administration-approved medication for MS that treats impaired ambulation by enhancing nerve conduction.

Glial cell injury and atrophied lesion volume as measures of chronic multiple sclerosis inflammation.

Background: Atrophied lesion volume (aLV), a proposed biomarker of disability progression in multiple sclerosis (MS) and transition into progressive MS (PMS), depicts chronic periventricular white matter (WM) pathology. Meningeal infiltrates, imaged as leptomeningeal contrast enhancement (LMCE), are linked with greater cortical pathology.

Objectives: To determine the relationship between serum-derived proteomic data with the development of aLV and LMCE in a heterogeneous group of people with MS (pwMS).

Neuroimaging assessment of facility-bound severely-affected MS reveals the critical role of cortical gray matter pathology: results from the CASA-MS case-controlled study.

Background: A subgroup of people with multiple sclerosis (pwMS) will develop severe disability. The pathophysiology underlying severe MS is unknown. The comprehensive assessment of severely affected MS (CASA-MS) was a case-controlled study that compared severely disabled in skilled nursing (SD/SN) (EDSS ≥ 7.

Choroid plexus enlargement is associated with future periventricular neurodegeneration in multiple sclerosis.

Background: The choroid plexus (CP), located within the ventricles of the brain and the primary producer of cerebrospinal fluid, has been shown to be enlarged in patients with multiple sclerosis (MS) and linked to periventricular remyelination failure. Atrophied T2-lesion volume (aT2-LV), a promising neurodegenerative imaging marker in progressive MS (PMS), reflects the volume of periventricular lesions subsumed into cerebrospinal fluid over the follow-up.

Methods: In a cohort of 143 people with relapsing-remitting MS (RRMS) and 53 with PMS, we used 3T magnetic resonance imaging (MRI) to quantify CP volume (CPV) at baseline and aT2-LV over an average of 5.