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Progressive multifocal leukoencephalopathy (PML) is a devastating infectious disease of the brain that is caused by JC virus (JCV) in the context of cellular immunodeficiency. To date, no effective antiviral [...]

Background and purpose: Data from neuro‐imaging techniques allow us to estimate a brain's age. Brain age is easily interpretable as 'how old the brain looks' and could therefore be an attractive communication tool for brain health in clinical practice. This study aimed to investigate its clinical utility by investigating the relationship between brain age and cognitive performance in multiple sclerosis (MS). Methods: A linear regression model was trained to predict age from brain magnetic resonance imaging volumetric features and sex in a healthy control dataset (HC_train, n = 1673). This model was used to predict brain age in two test sets: HC_test (n = 50) and MS_test (n = 201). Brain‐predicted age difference (BPAD) was calculated as BPAD = brain age minus chronological age. Cognitive performance was assessed by the Symbol Digit Modalities Test (SDMT). Results: Brain age was significantly related to SDMT scores in the MS_test dataset (r = −0.46, p < 0.001) and contributed uniquely to variance in SDMT beyond chronological age, reflected by a significant correlation between BPAD and SDMT (r = −0.24, p < 0.001) and a significant weight (−0.25, p = 0.002) in a multivariate regression equation with age. Conclusions: Brain age is a candidate biomarker for cognitive dysfunction in MS and an easy to grasp metric for brain health. [ABSTRACT FROM AUTHOR]

Motor Evoked Potentials (MEPs) are used to monitor disability progression in multiple sclerosis (MS). Their morphology plays an important role in this process. Currently, however, there is no clear definition of what constitutes a normal or abnormal morphology. To address this, five experts independently labeled the morphology (normal or abnormal) of the same set of 1,000 MEPs. The intra- and inter-rater agreement between the experts indicates they agree on the concept of morphology, but differ in their choice of threshold between normal and abnormal morphology. We subsequently performed an automated extraction of 5,943 time series features from the MEPs to identify a valid proxy for morphology, based on the provided labels. To do this, we compared the cross-validation performances of one-dimensional logistic regression models fitted to each of the features individually. We find that the approximate entropy (ApEn) feature can accurately reproduce the majority-vote labels. The performance of this feature is evaluated on an independent test set by comparing to the majority vote of the neurologists, obtaining an AUC score of 0.92. The model slightly outperforms the average neurologist at reproducing the neurologists consensus-vote labels. We can conclude that MEP morphology can be consistently defined by pooling the interpretations from multiple neurologists and that ApEn is a valid continuous score for this. Having an objective and reproducible MEP morphological abnormality score will allow researchers to include this feature in their models, without manual annotation becoming a bottleneck. This is crucial for large-scale, multi-center datasets. An exploratory analysis on a large single-center dataset shows that ApEn is potentially clinically useful. Introducing an automated, objective, and reproducible definition of morphology could help overcome some of the barriers that are currently obstructing broad adoption of evoked potentials in daily care and patient follow-up, such as standardization of measurements between different centers, and formulating guidelines for clinical use. [ABSTRACT FROM AUTHOR]

Highlights • TNFα blockers are highly effective and a therapeutic choice for several inflammatory diseases. • The widespread and long-term use of TNF-targeted therapies is associated with a growing number of paradoxical induced autoimmune processes. • NMOSD has never been reported in this context neither positive MOG IgG1. Abstract Tumor necrosis factor α (TNFα) inhibitors are highly effective and a therapeutic choice for several inflammatory diseases. Their broad and long-term use is associated with a growing number of paradoxical autoimmune events including demyelinating lesions of the central nervous system (CNS). We report and discuss a case of neuromyelitis optica spectrum disorder (NMOSD) with positive myelin oligodendrocyte glycoprotein antibodies (MOG-IgG1) following anti-TNFα therapy for a pustular psoriasis. [ABSTRACT FROM AUTHOR]

Background: Functional biomarkers able to identify multiple sclerosis (MS) patients at high risk of fast disability progression are lacking. The aim of this study was to evaluate the ability of multimodal (upper and lower limbs motor, visual, lower limbs somatosensory) evoked potentials (EP) to monitor disease course and identify patients exposed to unfavourable evolution.Methods: One hundred MS patients were assessed with visual, somatosensory and motor EP and rated on the Expanded Disability Status Scale (EDSS) at baseline (T0) and about 6 years later (T1). The Spearman correlation (rS) was used to evaluate the relationship between conventional EP scores and clinical findings. Multiple (logistic) regression analysis estimated the predictive value of baseline electrophysiological data for three clinical outcomes: EDSS, annual EDSS progression, and the risk of EDSS worsening.Results: In contrast to longitudinal correlations, cross-sectional correlations between the different EP scores and EDSS were all significant (0.33 ≤ rS < 0.67, p < 0.001). Baseline global EP score and EDSS were highly significant predictors (p < 0.0001) of EDSS progression 6 years later. The baseline global EP score was found to be an independent predictor of the EDSS annual progression rate (p < 0.001), and of the risk of disability progression over time (p < 0.005). Based on a ROC curve determination, we defined a Global EP Score cut off point (17/30) to identify patients at high risk of disability progression illustrated by a positive predictive value of 70%.Conclusion: This study provides a proof of the concept that electrophysiology could be added to MRI and used as another complementary prognostic tool in MS patients. [ABSTRACT FROM AUTHOR]

Background: In the 2-year CARE-MS trials (trial registration: NCT00530348; NCT00548405), alemtuzumab (12 mg/day; baseline: 5 days; 12 months later: 3 days) significantly improved clinical/magnetic resonance imaging outcomes vs subcutaneous interferon beta-1a in patients with relapsing-remitting multiple sclerosis (RRMS). Efficacy in alemtuzumab-treated patients was maintained through year 9 in 2 consecutive extension studies (NCT00930553; NCT02255656 [TOPAZ]). Objectives: To evaluate the status of disability over 9 years in pooled CARE-MS patients who had either 6-month confirmed disability improvement (CDI) or 6-month confirmed disability worsening (CDW) by years 2 or 9. Methods: Alemtuzumab-treated CARE-MS patients with baseline Expanded Disability Status Scale (EDSS) score ≥2 were stratified into 3 subgroups: with CDI, with CDW, or with stable disability. CDI and CDW were defined as ≥1-point decrease and increase, respectively, in EDSS score from core study baseline confirmed over 6 months. Improved and stable EDSS scores each year were defined as ≥1-point decrease and ≤0.5-point change in either direction, respectively, from core study baseline in available patients. Results: 511/811 (63%) alemtuzumab-treated patients had baseline EDSS score ≥2. Of these, 222 (43%) patients had 365 unique CDI events and 172 (34%) patients had 217 CDW events at any time during the 9-year study; 31 (6%) had both CDI and CDW. Few patients (n = 12) had a CDW event after CDI. Of patients with CDI at any time over 9 years, mean EDSS score change was --0.58 at year 9 vs core study baseline, and 51% had lower EDSS scores at year 9. Similar EDSS outcomes were observed at year 9 in the subset of patients who achieved CDI within the first 2 years of the study. However, patients with CDW any time over 9 years had worsened disability at year 9, with a +1.71 mean change in EDSS score from core study baseline; patients with CDW in the first 2 years of the study had a +2.27 EDSS score change by year 9. EDSS scores remained stable at 9 years (mean change, --0.10) in the 148 (29%) patients who had neither CDI nor CDW. Compared with previous years, no new safety signals were identified in year 9 in CARE-MS extension study patients. Conclusions: Achievement of CDI at any point in the CARE-MS studies was associated with improved disability at year 9 vs baseline. However, those with CDW had increased disability over 9 years regardless of when worsening occurred. These findings suggest that both CDI and CDW are meaningful end points for predicting long-term disability outcomes in patients with RRMS. [ABSTRACT FROM AUTHOR]

The stability of cerebral glucose utilization was examined in nine right-handed, healthy men (age, 24.88±2.93 years) using positron emission tomography (PET) and the [F]-fluorodeoxyglucose (FDG) method. Each study was run twice at intervals of 1-12 weeks with the subject at rest. The average cerebral metabolic rate for glucose (CMRGlu) was 5.40±0.71 mg/100 g per min (coefficient of variance, 13.08). The average intraindividual variation of CMRGlu was 7.91%±15.46% ( P=0.13). Metabolic indices (MI: regional/mean cortical CMRGlu) were used to determine the regional cerebral metabolic distribution. The interindividual (coefficient of variance, 7.13) and intraindividual variabilities (average variation, −0.12%±8.76%) of MI were smaller than those of metabolic rates. No reproducible significant asymmetry was observed. The FDG method used with subjects at rest thus yields low intraindividual variability of both cerebral glucose consumption and regional metabolic distribution, even at an interval of several weeks. Cerebral glucose utilization measured under such conditions may act as a reliable reference for determination of the influences of physiological (activation), pharmacological or pathological processes on cerebral glucose metabolism. [ABSTRACT FROM AUTHOR]

Objectives: Conventional MRI is not sensitive to many pathological processes underpinning multiple sclerosis (MS) ongoing in normal appearing brain tissue (NABT). Quantitative MRI (qMRI) and a multiparameter mapping (MPM) protocol are used to simultaneously quantify magnetization transfer (MT) saturation, transverse relaxation rate R2* (1/T2*) and longitudinal relaxation rate R1 (1/T1), and assess differences in NABT microstructure between MS patients and healthy controls (HC)., Methods: This prospective cross-sectional study involves 36 MS patients (21 females, 15 males; age range 22-63 years; 15 relapsing-remitting MS - RRMS; 21 primary or secondary progressive MS - PMS) and 36 age-matched HC (20 females, 16 males); age range 21-61 years). The qMRI maps are computed and segmented in lesions and 3 normal appearing cerebral tissue classes: normal appearing cortical grey matter (NACGM), normal appearing deep grey matter (NADGM), normal appearing white matter (NAWM). Individual median values are extracted for each tissue class and MR parameter. MANOVAs and stepwise regressions assess differences between patients and HC., Results: MS patients are characterized by a decrease in MT, R2* and R1 within NACGM (p < .0001) and NAWM (p < .0001). In NADGM, MT decreases (p < .0001) but R2* and R1 remain normal. These observations tend to be more pronounced in PMS. Quantitative MRI parameters are independent predictors of clinical status: EDSS is significantly related to R1 in NACGM and R2* in NADGM; the latter also predicts motor score. Cognitive score is best predicted by MT parameter within lesions., Conclusions: Multiparametric data of brain microstructure concord with the literature, predict clinical performance and suggest a diffuse reduction in myelin and/or iron content within NABT of MS patients., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)