Multiple Sclerosis Journal

IntroductionMultiple sclerosis (MS) is a chronic neuroinflammatory and neurodegenerative disease. MS prevalence varies geographically and is notably high in Scotland. Disease trajectory varies significantly between individuals and the causes for this are largely unclear. Biomarkers predictive of disease course are urgently needed to allow improved stratification for current disease modifying therapies and future targeted treatments aimed at neuroprotection and remyelination. MRI can detect disea...

We investigated performance validity tests (PVTs) in patients presenting with new onset cognitive complaints associated with post-acute sequelae of COVID-19 infection (PASC). Retrospective data were obtained from IRB-approved registries. All patients completed the Victoria Symptom Validity Test (VSVT) in conjunction with a neuropsychological evaluation. A sub-analysis included 7 other PVT measures. The PASC sample was compared to an analogous multiple sclerosis (MS) sample with known PVT failure...

BackgroundNatalizumab is a high-efficacy therapy for RRMS. While EID may reduce PML risk, critical gaps persist in understanding post-cessation outcomes, posing urgent clinical challenges for neurologists discontinuing treatment. ObjectivesTo compare efficacy/safety of natalizumab SID vs. EID and quantify relapse/disability risk after cessation in adults with RRMS. MethodsWe conducted a systematic review/meta-analysis (PROSPERO: CRD420251103014) following PRISMA guidelines. We searched MEDLINE...

BackgroundTreatment strategy for relapsing multiple sclerosis (RMS) is increasingly shifting towards first-line use of high-efficacy DMT (H-DMT). However, DMT efficacy declines with increasing age and the benefit of first line H-DMT at higher age remains unclear. Here, we aimed to investigate whether the superiority of H-DMT over moderate-efficacy DMT (M-DMT) depends on age. MethodsUsing the Austrian MS database, we included previously DMT-naive RMS patients aged [≥]18 years, who i) initiate...

BackgroundOcrelizumab and natalizumab are commonly prescribed high-effectiveness disease-modifying therapies (DMTs) for relapsing-remitting multiple sclerosis (RRMS). However, no randomized clinical trial and few real-world studies have directly compared their effectiveness in reducing disability progression. Subtype classification and disability status are critical for multiple sclerosis (MS) research, but these data are often missing in electronic health records (EHRs), limiting robust real-wo...

BackgroundSlowly Expanding Lesions (SELs) in Multiple Sclerosis (MS) are markers of chronic active lesions and seem to trigger disability. This study aimed to analyse spatial features of SELs through diffusion MRI and their clinical impact on progression independent of relapse activity (PIRA). MethodsAn observational study of MS subjects prospectively followed since 2011; inclusion required at least three longitudinal T1/T2-weighted and diffusion-weighted MRIs. Subjects followed clinical assess...

BackgroundParamagnetic rim lesions (PRL) are an emerging biomarker for multiple sclerosis (MS). In addition to associating with greater disease severity, PRL may be diagnostically supportive. ObjectiveOur aim was to determine PRL specificity and sensitivity for discriminating MS from its diagnostic mimics using real-world clinical diagnostic and imaging data. MethodsThis is a retrospective, cross-sectional analysis of a longitudinal cohort of patients with prospectively collected observational...

BackgroundMultiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) share overlapping clinical and imaging features, complicating differential diagnosis. The choroid plexus is increasingly recognized as a regulator of neuroinflammation and may play a critical role in the pathogenesis and differentiation of these conditions. Choroid plexus cysts (CPCs) are difficult to detect with conventional MRI resolution and standard anatomical approaches. High-resolution 7T MRI enables their...

BackgroundClinically defined relapses are the traditional primary endpoint of randomized control trials (RCTs) in multiple sclerosis (MS), yet a substantial proportion lack new inflammatory lesions. Confirming relapses with brain and spinal cord MRI to distinguish relapses with active MRI (RAM) from acute clinical events with stable MRI (ACES) may provide a more sensitive primary outcome for future trials. ObjectiveTo estimate RAM and ACES rates in MS trials and evaluate the impact on statistic...

BackgroundChronic active MS lesions with paramagnetic rim can be identified by high-pass filtered (HPF) phase imaging or quantitative susceptibility mapping (QSM). PurposeThe objective was to compare the ability of HPF and QSM to identify MS lesions with greater myelin damage and to distinguish MS patients with increased clinical disability. Material and MethodsEighty-six patients were scanned with gradient echo sequence for lesion rim detection and FAST-T2 sequence for myelin water fraction (...

Background and ObjectivesWolfram syndrome (WFS) is a genetic disorder mainly caused by pathogenic variants in the WFS1 gene. It is characterized clinically by optic atrophy (OA), diabetes mellitus (DM), sensorineural hearing loss (SNHL), diabetes insipidus (DI), and variable neurological/psychiatric symptoms. WFS typically manifests before age 20 and progresses into adulthood. Classical neuroradiological features include cerebellar and/or brainstem atrophy as well as white matter abnormalities r...

ObjectiveTo evaluate how within-person changes in accelerometry-derived activity patterns translate to brain atrophy and disability worsening in people with multiple sclerosis (PwMS). MethodsWe included PwMS aged [≥]40 years with approximately annual brain MRI who wore GT9X Actigraph accelerometers every three months over three years. Accelerometry-derived indices included total and 2-hour specific activity, sedentary time, and circadian rhythm parameters. Confirmed disability worsening was ...

Spinal cord pathology is a major determinant of irreversible disability in progressive multiple sclerosis. The demyelinated lesion is a cardinal feature. The well-characterised anatomy of the spinal cord and new analytic approaches allows the systematic study of lesion topography and its extent of inflammatory activity unveiling new insights into disease pathogenesis. We studied cervical, thoracic, and lumbar spinal cord tissue from 119 pathologically confirmed multiple sclerosis cases. Immunohi...

BackgroundGrey matter (GM) atrophy has been suggested as the most accurate marker of neurodegeneration in multiple sclerosis (MS) progression. However, long-term comparisons between MS and healthy controls (HC) are rare, and the most significantly atrophying brain regions and their clinical importance still need robust and longitudinal validation. MethodsThis multi-cohort longitudinal observational study used two relapsing remitting MS (RRMS) cohorts (N=386, T1w-scans=940) sampled for up to 12 ...

Modern management of MS targets No Evidence of Disease Activity (NEDA): no clinical relapses, no magnetic resonance imaging (MRI) disease activity and no disability worsening. While MRI is the principal tool available to neurologists for monitoring clinically silent MS disease activity and, where appropriate, escalating treatment, standard radiology reports are qualitative and may be insensitive to the development of new or enlarging lesions. Existing quantitative neuroimaging tools lack adequat...

Neuromyelitis optica associated with aquaporin-4-antibodies (NMOSD-AQP4) and myelin oligodentrocyte-glycoprotein antibody-associated disorder (MOGAD) have been recently recognised as different from multiple sclerosis. Although conventional MRI may help distinguish multiple sclerosis from antibody-mediated diseases, the use of quantitative and non-conventional imaging may give more pathological information and explain the clinical differences. We compared, using non-conventional imaging, brain ...

ObjectivesPeople with Multiple Sclerosis (MS) have a larger choroid plexus (CP) volume than healthy controls. We investigated CP volume in early MS by quantitatively assessing brain MRI scans in patients presenting with optic neuritis (ON) as a clinically isolated syndrome (CIS), compared to a cohort with established Relapsing Remitting Multiple Sclerosis (RRMS) and healthy controls. MethodsPre- and post-gadolinium 3D-T1, 3D FLAIR and diffusion-weighted images were acquired from 44 CIS ON patie...

Background/PurposeLeptomeningeal enhancement (LME) on post-contrast FLAIR is described as a potential biomarker of meningeal inflammation in multiple sclerosis (MS). Here we report a comprehensive assessment of the impact of MRI field strength and acquisition timing on meningeal contrast enhancement (MCE). MethodsThis was a cross-sectional, observational study of 95 participants with MS and 17 healthy controls (HC) subjects. Each participant underwent an MRI of the brain on both a 7 Tesla (7T) ...

IntroductionCortical grey (CoGM) and white matter (WM) microglial activation (MA) is involved in the pathogenesis of multiple sclerosis (MS). [F-18]PBR06 positron emission tomography (PET) targeting 18kilodalton-translocator protein (TSPO) can detect abnormal MA in MS. Aims and ObjectivesThe goal of this study is to determine the effect of disease modifying treatment (DMT) efficacy on modulating the extent and clinical and radiological correlates of MA in MS patients. MethodsThirty [F-18]PBR06...

BackgroundIn multiple sclerosis (MS), 7 Tesla (7T) MRI improves the visualization of cortical (CLs) and white matter (WM) lesions with a paramagnetic rim (PRLs), associated with smoldering inflammation. Spinal cord (SC) atrophy is a critical determinant of clinical disability in MS, but its importance relative to PRLs and CLs in predicting neurological disability remains unclear. PurposeTo identify the most relevant predictors for baseline neurological disability and 4-year disease progression ...