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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. Initially characterized in autopsy specimens, multiple approaches to visualize chronic active lesions (CALs) in vivo using advanced neuroimaging techniques and postprocessing methods are rapidly emerging. Among these in vivo imaging correlates of CALs, paramagnetic rim lesions (PRLs) are defined by the presence of a perilesional rim formed by iron-laden microglia and macrophages, whereas slowly expanding lesions are identified based on linear, concentric lesion expansion over time. In recent years, several longitudinal studies have linked the occurrence of in vivo detected CALs to a more aggressive disease course. PRLs are highly specific to MS and therefore have recently been incorporated into the MS diagnostic criteria. They also have prognostic potential as biomarkers to identify patients at risk of early and severe disease progression. These developments could significantly affect MS care and the evaluation of new treatments. This review describes the latest knowledge on CAL biology and imaging and the relevance of CALs to the natural history of MS. In addition, we outline considerations for current and future in vivo biomarkers of CALs, emphasizing the need for validation, standardization, and automation in their assessment. [ABSTRACT FROM AUTHOR]

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." Results: In 30 pwMS, 59 PRLs, 74 DSHLs, and 107 SILs were identified. Beside longer T1 relaxation times of PRLs compared to DSHLs and SILs (2030.5 (1519–2540) vs 1615.8 (1403.3–1953.5) vs 1199.5 (1089.6–1334.6), both p < 0.001), longer T1 relaxation times were observed in the PRL PPA compared to the SIL PPA and the NAWM but not the DSHL PPA. Patients with secondary progressive multiple sclerosis (SPMS) had longer T1 relaxation times in PRLs compared to patients with late relapsing multiple sclerosis (lRMS) (2394.5 (2030.5–3040) vs 1869.3 (1491.4–2451.3), p = 0.015) and also in the PRL PPA compared to patients with early relapsing multiple sclerosis (eRMS) (982 (927–1093.5) vs 904.3 (793.3–958.5), p = 0.013). Conclusion: PRLs are more destructive than SILs, leading to diffuse periplaque white matter (WM) damage. The quantitative MRI-based evaluation of the PRL PPA could be a marker for silent progression in pwMS. [ABSTRACT FROM AUTHOR]

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). Methods: In this cross-sectional retrospective study, we included pwMS with both 3T brain MRI and an OCT scan. Regression models were calculated with OCT parameters (pRNFL, GCIPL, INL) as dependent variables, and the number of PRLs as an independent variable adjusted for covariates. Results: We analyzed data from 107 pwMS (mean age 34.7 years (SD 10.9), 64.5% female, median disease duration 6 years (IQR 1–13), median EDSS 1.5 (range 0–6.5)). Higher number of PRLs was associated with lower pRNFL (β = −0.18; 95% CI −0.98, −0.03; p = 0.038) and GCIPL thickness (β = −0.21; 95% CI −0.58, −0.02; p = 0.039). Conclusion: The association between higher number of PRLs and lower pRNFL and GCIPL thicknesses provides additional evidence that pwMS with PRLs are affected by a more pronounced neurodegenerative process. [ABSTRACT FROM AUTHOR]

Progressive multiple sclerosis patients show substantial lesion activity that correlates with clinical disease severity and sex: a retrospective autopsy cohort analysis. Slowly expanding lesions are a marker of progressive MS - Yes About 20 years ago, John Prineas and colleagues described the neuropathology of "chronic active/slowly expanding lesions" in secondary progressive multiple sclerosis (MS) autopsy cases pointing out their potential pathogenetic relevance to disease progression in MS. [Extracted from the article]

Background: Despite strongly overlapping patterns of clinical and histopathologic findings in primary and secondary progressive multiple sclerosis, differences concerning motor symptoms, central nervous system inflammation, atrophy, and demyelination that cannot be accounted for by lesion load alone remain to be elucidated. Purpose: To evaluate the normal-appearing deep gray matter in patients with primary and secondary progressive multiple sclerosis, diffusion tensor imaging was used in this study. Material and Methods: In 14 multiple sclerosis patients with primary and secondary progressive multiple sclerosis, axial echo-planar single-shot diffusion tensor imaging sequences with 32 diffusion-encoding directions and axial FLAIR sequences were acquired on a 3T system using an eight-channel SENSE head coil. FLAIR hyperintense multiple sclerosis lesions were outlined semi-automatically and normal-appearing deep gray matter was outlined manually (caudate nucleus, globus pallidus, putamen, thalamus, substantia nigra, and red nucleus). Fractional anisotropy and mean diffusivity values within the normal-appearing deep gray matter for the two groups were compared. Results: Interhemispheric differences in mean diffusivity values (but not in fractional anisotropy), were significantly higher in primary progressive multiple sclerosis than in secondary progressive multiple sclerosis for the substantia nigra (P = 0.04) and the putamen (P = 0.021). Volumes, mean diffusivity, or fractional anisotropy of the remaining normal-appearing deep gray matter did not differ significantly. Conclusion: This study showed a higher interhemispheric difference in the mean diffusivity in the substantia nigra and putamen in patients with primary progressive multiple sclerosis than in those with secondary progressive multiple sclerosis. These changes may represent edema, as well as axonal and myelin loss that can affect the normal-appearing deep gray matter of the two hemispheres differently and may point to differences in the laterality of motor symptoms. [ABSTRACT FROM AUTHOR]