BACKGROUND AND PURPOSE: Previous studies have suggested that the central vein sign and iron rims are specific features of MS lesions. Using 3T SWI, we aimed to compare the frequency of lesions with central veins and iron rims in patients with clinically isolated syndrome and MS-mimicking disorders and test their diagnostic value in predicting conversion from clinically isolated syndrome to MS. MATERIALS AND METHODS: For each patient, we calculated the number of brain lesions with central veins and iron rims. We then identified a simple rule involving an absolute number of lesions with central veins and iron rims to predict conversion from clinically isolated syndrome to MS. Additionally, we tested the diagnostic performance of central veins and iron rims when combined with evidence of dissemination in space. RESULTS: We included 112 patients with clinically isolated syndrome and 35 patients with MS-mimicking conditions. At follow-up, 94 patients with clinically isolated syndrome developed MS according to the 2017 McDonald criteria. Patients with clinically isolated syndrome had a median of 2 central veins (range, 0–19), while the non-MS group had a median of 1 central vein (range, 0–6). Fifty-six percent of patients who developed MS had ≥1 iron rim, and none of the patients without MS had iron rims. The sensitivity and specificity of finding ≥3 central veins and/or ≥1 iron rim were 70% and 86%, respectively. In combination with evidence of dissemination in space, the 2 imaging markers had higher specificity than dissemination in space and positive findings of oligoclonal bands currently used to support the diagnosis of MS. CONCLUSIONS: A single 3T SWI scan offers valuable diagnostic information, which has the potential to prevent MS misdiagnosis.

Background: The central vein sign (CVS) is a radiological feature proposed as a multiple sclerosis (MS) imaging biomarker able to accurately differentiate MS from other white matter diseases of the central nervous system. In this work, we evaluated the pooled proportion of the CVS in brain MS lesions and to estimate the diagnostic performance of CVS to perform a diagnosis of MS and propose an optimal cut-off value. Methods: A systematic search was performed on publicly available databases (PUBMED/MEDLINE and Web of Science) up to 24 August 2020. Analysis of the proportion of white matter MS lesions with a central vein was performed using bivariate random-effect models. A meta-regression analysis was performed and the impact of using particular sequences (such as 3D echo-planar imaging) and post-processing techniques (such as FLAIR*) was investigated. Pooled sensibility and specificity were estimated using bivariate models and meta-regression was performed to address heterogeneity. Inclusion and publication bias were assessed using asymmetry tests and a funnel plot. A hierarchical summary receiver operating curve (HSROC) was used to estimate the summary accuracy in diagnostic performance. The Youden index was employed to estimate the optimal cut-off value using individual patient data. Results: The pooled proportion of lesions showing a CVS in the MS population was 73%. The use of the CVS showed a remarkable diagnostic performance in MS cases, providing a pooled specificity of 92% and a sensitivity of 95%. The optimal cut-off value obtained from the individual patient data pooled together was 40% with excellent accuracy calculated by the area under the ROC (0.946). The 3D-EPI sequences showed both a higher pooled proportion compared to other sequences and explained heterogeneity in the meta-regression analysis of diagnostic performances. The 1.5 Tesla (T) scanners showed a lower (58%) proportion of MS lesions with a CVS compared to both 3T (74%) and 7T (82%). Conclusions: The meta-analysis we have performed shows that the use of the CVS in differentiating MS from other mimicking diseases is encouraged; moreover, the use of dedicated sequences such as 3D-EPI and the high MRI field is beneficial.

Background and Objectives To evaluate the extent of intrathecal inflammation in patients with primary progressive MS (PPMS) at the time of diagnosis and to define markers and a specific inflammatory profile capable of distinguishing progressive from relapsing-remitting multiple sclerosis (RRMS). Methods Levels of 34 pro- and anti-inflammatory cytokines and chemokines in the CSF were evaluated at the diagnosis in 16 patients with PPMS and 80 with RRMS. All patients underwent clinical evaluation, including Expanded Disability Status Scale assessment and a 3T brain MRI to detect white matter and cortical lesion number and volume and global and regional cortical thickness. Results Higher levels of CXCL12 (odds ratio [OR] = 3.97, 95% CI [1.34–11.7]) and the monocyte-related osteopontin (OR = 2.24, 95% CI [1.01–4.99]) were detected in patients with PPMS, whereas levels of interleukin-10 (IL10) (OR = 0.28, 95% CI [0.09–0.96]) were significantly increased in those with RRMS. High CXCL12 levels were detected in patients with increased gray matter lesion number and volume (p = 0.001, r = 0.832 and r = 0.821, respectively). Pathway analysis confirmed the chronic inflammatory processes occurring in PPMS. Conclusions At the time of diagnosis, a specific CSF protein profile can recognize the presence of early intrathecal inflammatory processes, possibly stratifying PPMS with respect to RRMS. Elevated CSF levels of CXCL12 and osteopontin suggested a key role of brain innate immunity and glia activity in MS. These molecules could represent useful candidate markers of MS progression, with implications for the pathogenesis and treatment of progressive MS. Classification of Evidence This study provides Class III evidence that CXCL12 and monocyte-related osteopontin may be correlated with PPMS, and IL-10 may be related to RRMS. It is may be correlated due to Bonferroni correction negating the statistical correlations found in the study.

Background and purpose: Although cognitive impairment (CI) is frequent in multiple sclerosis (MS) patients, few studies (and with conflicting results) have evaluated early predictors of CI in the long term. We aimed at determining associations between early clinical/neuroradiological variables with reference to CI after 20 years of MS.Methods: We investigated in 170 MS patients the relationship between clinical/magnetic resonance imaging (MRI) data at diagnosis and cognitive status almost 20 years after MS onset. Among others, number and volume of both white matter lesions (WMLs) and cortical lesions (CLs) were evaluated at diagnosis and after 2 years. All MS patients were followed over time and underwent a comprehensive neuropsychological assessment at the end of study. Advanced statistical methods (unsupervised cluster analysis and random forest model) were conducted.Results: CI patients showed higher focal cortical pathology at diagnosis compared to cognitively normal subjects (p < 0.001). Volumes of both WMLs and CLs emerged as the MRI metrics most associated with long‐term CI. Moreover, number of CLs (especially ≥3) was also strongly associated with long‐term CI (≥3 CLs: odds ratio [OR] = 3.7, 95% confidence interval = 1.8–7.5, p < 0.001), more than number of WMLs; the optimal cutoff of three CLs (area under the curve = 0.67, specificity = 75%, sensitivity = 55%) was estimated according to the risk of developing CI.Conclusions: These results highlight the impact of considering both white and gray matter focal damage from early MS stages. Given the low predictive value of WML number and the poor clinical applicability of lesion volume estimation in the daily clinical context, the evaluation of number of CLs could represent a reliable prognostic marker of CI.

• So far, the prevalence of COVID-19 in multiple sclerosis patients are unknown. • The prevalence in an MS cohort from the Veneto region, Italy, was higher than in the general population. The disease course was mild to moderate. • MS-population based studies could be a good way to investigate indirectly the infection prevalence in the general population.

The aim of the study is to investigate the impact of coping strategies on Health-Related Quality of Life (HRQoL) and physical disability assessed with the Expanded Disability Status Scale (EDSS) of people with multiple sclerosis (pwMS). PwMS were asked to focus on “MS diagnosis” as the core stressor. One hundred eight pwMS completed the Coping Responses Inventory-Adult form (CRI-Adult), the Multiple Sclerosis Quality of Life-29 (MSQoL-29), and the Depression Anxiety Stress Scale-21 (DASS-21). Multiple regression analyses (first block: EDSS, disease duration, and DASS-21) revealed that physical MSQoL-29 was positively associated with Alternative Rewards and negatively with Resigned Acceptance of the CRI-Adult. The mental MSQoL-29 was positively associated with Problem-Solving and negatively with Emotional Discharge. The Expanded Disability Status Scale (EDSS; first block: disease duration and general distress) was negatively associated with Positive Reappraisal. The Analysis of covariance (ANCOVA) revealed that pwMS with lower physical disability showed higher scores in Positive Reappraisal and lower scores in Emotional Discharge than pwMS with a higher physical disability. Coping strategies can play a role on HRQoL and physical disability in pwMS above and beyond EDSS, disease duration, and general distress. Psychological interventions should be considered in pwMS since the time of diagnosis to promote engagement in adaptive coping strategies and contrast the maladaptive ones.