Chronic active lesions in multiple sclerosis: classification, terminology, and clinical significance.

In multiple sclerosis (MS), increasing disability is considered to occur due to persistent, chronic inflammation trapped within the central nervous system (CNS). This condition, known as smoldering neuroinflammation, is present across the clinical spectrum of MS and is currently understood to be relatively resistant to treatment with existing disease-modifying therapies. Chronic active white matter lesions represent a key component of smoldering neuroinflammation.

Paramagnetic rim lesions are associated with inner retinal layer thinning and progression independent of relapse activity in multiple sclerosis.

Background And Purpose: Paramagnetic rim lesions (PRLs) are chronic active lesions associated with a severe disease course in multiple sclerosis (MS). This study was undertaken to investigate an association between retinal layer thinning (annualized loss of peripapillary retinal nerve fiber layer [aLpRNFL] and ganglion cell-inner plexiform layer [aLGCIPL]) and PRLs in patients with MS (pwMS).

Methods: In this study, pwMS with brain magnetic resonance imaging and ≥2 optical coherence tomography scans were included.

Novel and Emerging Treatments to Target Pathophysiological Mechanisms in Various Phenotypes of Multiple Sclerosis.

The objective is to comprehensively review novel pharmacotherapies used in multiple sclerosis (MS) and the possibilities they may carry for therapeutic improvement. Specifically, we discuss pathophysiological mechanisms worth targeting in MS, ranging from well known targets, such as autoinflammation and demyelination, to more novel and advanced targets, such as neuroaxonal damage and repair. To set the stage, a brief overview of clinical MS phenotypes is provided, followed by a comprehensive recapitulation of both clinical and paraclinical outcomes available to assess the effectiveness of treatments in achieving these targets.

Super-resolution QSM in little or no additional time for imaging (NATIve) using 2D EPI imaging in 3 orthogonal planes.

Quantitative Susceptibility Mapping has the potential to provide additional insights into neurological diseases but is typically based on a quite long (5-10 min) 3D gradient-echo scan which is highly sensitive to motion. We propose an ultra-fast acquisition based on three orthogonal (sagittal, coronal and axial) 2D simultaneous multi-slice EPI scans with 1 mm in-plane resolution and 3 mm thick slices. Images in each orientation are corrected for susceptibility-related distortions and co-registered with an iterative non-linear Minimum Deformation Averaging (Volgenmodel) approach to generate a high SNR, super-resolution data set with an isotropic resolution of close to 1 mm.

Metabolic Insights into Iron Deposition in Relapsing-Remitting Multiple Sclerosis via 7 T Magnetic Resonance Spectroscopic Imaging.

Objective: To investigate the metabolic pattern of different types of iron accumulation in multiple sclerosis (MS) lesions, and compare metabolic alterations within and at the periphery of lesions and newly emerging lesions in vivo according to iron deposition.

Methods: 7 T MR spectroscopic imaging and susceptibility-weighted imaging was performed in 31 patients with relapsing-remitting MS (16 female/15 male; mean age, 36.9 ± 10.

Myeloid cell iron uptake pathways and paramagnetic rim formation in multiple sclerosis.

In multiple sclerosis (MS), sustained inflammatory activity can be visualized by iron-sensitive magnetic resonance imaging (MRI) at the edges of chronic lesions. These paramagnetic rim lesions (PRLs) are associated with clinical worsening, although the cell type-specific and molecular pathways of iron uptake and metabolism are not well known. We studied two postmortem cohorts: an exploratory formalin-fixed paraffin-embedded (FFPE) tissue cohort of 18 controls and 24 MS cases and a confirmatory snap-frozen cohort of 6 controls and 14 MS cases.

Paramagnetic rim lesions lead to pronounced diffuse periplaque white matter damage in multiple sclerosis.

Background: Paramagnetic rim lesions (PRLs) are an imaging biomarker in multiple sclerosis (MS), associated with a more severe disease.

Objectives: To determine quantitative magnetic resonance imaging (MRI) metrics of PRLs, lesions with diffuse susceptibility-weighted imaging (SWI)-hypointense signal (DSHLs) and SWI-isointense lesions (SILs), their surrounding periplaque area (PPA) and the normal-appearing white matter (NAWM).

Methods: In a cross-sectional study, quantitative MRI metrics were measured in people with multiple sclerosis (pwMS) using the multi-dynamic multi-echo (MDME) sequence post-processing software "SyMRI.

Ultrahigh-field MRI: where it really makes a difference.

Background: Currently, two major magnetic resonance (MR) vendors provide commercial 7‑T scanners that are approved by the Food and Drug Administration (FDA) for clinical application. There is growing interest in ultrahigh-field MRI because of the improved clinical results in terms of morphological detail, as well as functional and metabolic imaging capabilities.

Materials And Methods: The 7‑T systems benefit from a higher signal-to-noise ratio, which scales supralinearly with field strength, a supralinear increase in the blood oxygenation level dependent (BOLD) contrast for functional MRI and susceptibility weighted imaging (SWI), and the chemical shift increases linearly with field strength with consequently higher spectral resolution.

Association of paramagnetic rim lesions and retinal layer thickness in patients with multiple sclerosis.

Background: Paramagnetic rim lesions (PRLs) are chronic active lesions associated with a more severe disease course in multiple sclerosis (MS). Retinal layer thinning measured by optical coherence tomography (OCT) is a biomarker of neuroaxonal damage associated with disability progression in MS.

Objective: We aimed to determine a potential association between OCT parameters (peripapillary retinal nerve fiber layer (pRNFL) ganglion cell-inner plexiform layer (GCIPL), inner nuclear layer (INL) thickness), and PRLs in patients with MS (pwMS).

A case of primary optic pathway demyelination caused by oncocytic oligodendrogliopathy of unknown origin.

We report the case of a 22-year-old woman presenting with an acute onset of dizziness, gait dysbalance and blurred vision. Magnetic resonance imaging included 3 Tesla and 7 Tesla imaging and revealed a T2-hyperintense, T1-hypointense, non-contrast-enhancing lesion strictly confined to the white matter affecting the right optic radiation. An extensive ophthalmologic examination yielded mild quadrantanopia but no signs of optic neuropathy.

Lesion-Specific Metabolic Alterations in Relapsing-Remitting Multiple Sclerosis Via 7 T Magnetic Resonance Spectroscopic Imaging.

Background: Magnetic resonance spectroscopic imaging (MRSI) of the brain enables in vivo assessment of metabolic alterations in multiple sclerosis (MS). This provides complementary insights into lesion pathology that cannot be obtained via T1- and T2-weighted conventional magnetic resonance imaging (cMRI).

Purpose: The aims of this study were to assess focal metabolic alterations inside and at the periphery of lesions that are visible or invisible on cMRI, and to correlate their metabolic changes with T1 hypointensity and the distance of lesions to cortical gray matter (GM).

Peripheral Hemolysis in Relation to Iron Rim Presence and Brain Volume in Multiple Sclerosis.

Background: Iron rim lesions (IRLs) represent chronic lesion activity and are associated with a more severe disease course in multiple sclerosis (MS). How the iron rims around the lesions arise in patients with MS (pwMS), and whether peripheral hemolysis may be a source of iron in rim associated macrophages, is unclear.

Objective: To determine a potential correlation between peripheral hemolysis parameters and IRL presence in pwMS.

B Cell Depletion and SARS-CoV-2 Vaccine Responses in Neuroimmunologic Patients.

Objective: The study was undertaken to assess the impact of B cell depletion on humoral and cellular immune responses to severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccination in patients with various neuroimmunologic disorders on anti-CD20 therapy. This included an analysis of the T cell vaccine response to the SARS-CoV-2 Delta variant.

Methods: We investigated prospectively humoral and cellular responses to SARS-CoV-2 mRNA vaccination in 82 patients with neuroimmunologic disorders on anti-CD20 therapy and 82 age- and sex-matched healthy controls.

Extensive Brain Pathologic Alterations Detected with 7.0-T MR Spectroscopic Imaging Associated with Disability in Multiple Sclerosis.

Background MR spectroscopic imaging (MRSI) allows in vivo assessment of brain metabolism and is of special interest in multiple sclerosis (MS), where morphologic MRI cannot depict major parts of disease activity. Purpose To evaluate the ability of 7.0-T MRSI to depict and visualize pathologic alterations in the normal-appearing white matter (NAWM) and cortical gray matter (CGM) in participants with MS and to investigate their relation to disability.

Kurt Jellinger 90: his contribution to neuroimmunology.

This review honors Kurt Jellinger on his 90th birthday as one of the most outstanding neuropathologists, who has contributed immensely to neuroscience due to his vast experience and collection of excellently documented autopsy cases. Two of his many insightful reports are highlighted here. One report focuses on the pathogenesis of inflammatory demyelinating diseases and investigates the neuropathology in autopsy tissue of a patient, who developed an MS-like disease after repeated treatment with lyophilized bovine brain cells in 1958.

Long-term evolution of multiple sclerosis iron rim lesions in 7 T MRI.

Recent data suggest that multiple sclerosis white matter lesions surrounded by a rim of iron containing microglia, termed iron rim lesions, signify patients with more severe disease course and a propensity to develop progressive multiple sclerosis. So far, however, little is known regarding the dynamics of iron rim lesions over long-time follow-up. In a prospective longitudinal cohort study in 33 patients (17 females; 30 relapsing-remitting, three secondary progressive multiple sclerosis; median age 36.

Should I stop or should I go on? Disease modifying therapy after the first clinical episode of multiple sclerosis.

Introduction: Treatment with disease-modifying therapies (DMT) in patients with clinically isolated syndrome (CIS) represents standard care in multiple sclerosis (MS) patients nowadays. Since a proportion of patients may show no evidence of disease activity (NEDA) after some time of treatment, the question might arise about the risks of stopping DMT.

Methods: We present a cohort of 49 patients who started DMT immediately after CIS and had no evidence of disease activity (NEDA-3) for at least five years before discontinuation of therapy.

Cranial Nerve Enhancement in Multiple Sclerosis Is Associated With Younger Age at Onset and More Severe Disease.

The overall frequency of cranial nerve pathology, including cranial nerves other than the trigeminal nerve, as well as its relation to brainstem lesion formation on magnetic resonance imaging (MRI) and clinical correlates in multiple sclerosis (MS) is unknown. We aimed to determine the frequency of cranial nerve enhancement on MRI, and its association with brainstem lesion formation and clinical outcomes. We retrospectively analyzed, in 183 patients, (RRMS: 156, SPMS: 15, PPMS: 6, CIS: 6) 651 MRIs (76.

Do elevated autoantibodies in patients with multiple sclerosis matter?

Objectives: The incidence and clinical impact of serum autoantibodies in patients with multiple sclerosis (MS) are controversially discussed. The aim of the study was to reassess the value of elevated serum autoantibodies in our MS study cohort.

Material & Methods: In total, 176 MS patients were retrospectively analyzed for coexistence and clinical impact of increased serum autoantibody levels.

7 T Magnetic Resonance Spectroscopic Imaging in Multiple Sclerosis: How Does Spatial Resolution Affect the Detectability of Metabolic Changes in Brain Lesions?

Objectives: The aim of this study was to assess the utility of increased spatial resolution of magnetic resonance spectroscopic imaging (MRSI) at 7 T for the detection of neurochemical changes in multiple sclerosis (MS)-related brain lesions.

Materials And Methods: This prospective, institutional review board-approved study was performed in 20 relapsing-remitting MS patients (9 women/11 men; mean age ± standard deviation, 30.8 ± 7.

Iron related changes in MS lesions and their validity to characterize MS lesion types and dynamics with Ultra-high field magnetic resonance imaging.

Iron accumulates with age in the normal human brain. This process is altered at several levels in the brain of multiple sclerosis (MS) patients. Since iron is mainly stored in oligodendrocytes and myelin in the normal brain, its liberation in demyelinating lesions may amplify tissue damage in demyelinating lesions and its uptake in macrophages and microglia may help to more precisely define activity stages of the lesions.

Epidemiology of Multiple Sclerosis in Austria.

Background: To assess the incidence rate and prevalence ratio of multiple sclerosis (MS) in Austria.

Methods: Hospital discharge diagnosis and MS-specific immunomodulatory treatment prescriptions from public health insurances, covering 98% of Austrian citizens with health insurance were used to extrapolate incidence and prevalence numbers based on the capture-recapture method.

Results: A total of 1,392,629 medication prescriptions and 40,956 hospitalizations were extracted from 2 data sources, leading to a total of 13,205 patients.