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Introduction: Patients with Multiple Sclerosis (pwMS) treated with anti-CD20 (cluster of differentiation) monoclonal antibodies (mAbs) such as ocrelizumab (OCR) and ofatumumab (OFA) show a reduction mainly of B-lymphocytes, but also other lymphocyte subsets can be affected by these treatments. There is limited data on differences between lymphocyte subset counts of pwMS after treatment initiation with OCR or OFA. Objective: To compare lymphocyte subset counts after treatment initiation in pwMS treated with OCR and OFA. Methods: We analyzed 22 pwMS initiated on OFA and 56 sex-, age- and MS course matched pwMS initiated on OCR from 2 prospectively collected observational MS databases (Bern [n: OFA 14, OCR 44] and Vienna [n: OFA 8, OCR 12]) statistically comparing lymphocyte subset counts (Mann Whitney Test). Results: We found that pwMS treated with OCR showed a stronger reduction of CD20 B-lymphocytes (P =.001), and a trend towards lower counts of CD8+ T cells (P =.056) compared to pwMS treated with OFA, whereas reduction of total lymphocyte, CD4+ lymphocyte and NK cell count was equally distributed between both treatments. Conclusion: Different effects on lymphocyte subpopulations appear to be present in pwMS after treatment initiation with different anti-CD20 mAbs. Further studies are needed to determine potential effects on anti-CD20 treatment efficacy as well as treatment associated risks such as failed vaccinations and infections. [ABSTRACT FROM AUTHOR]

Background: Odour discrimination and identification (DI) are markers associated with disability worsening and neuroaxonal damage in multiple sclerosis (MS). Objective: The main objective of this research is to investigate whether longitudinal change of DI predicts long-term MS disease course. Methods: This is a 6-year prospective longitudinal study on MS patients at the MS Clinic Innsbruck. Clinical, bi-annual visits assessed patients' history and Expanded Disability Status Scale (EDSS) score. DI and cognitive function were assessed at baseline (BL), Year 1 (Y1), Year 2 (Y2) and Year 6 (Y6) by the 'Sniffin' Sticks'/Symbol Digit Modalities Test. Results: Around 92 of 139 patients were available for Y6 follow-up. Mean DI scores significantly decreased over time (BL = 27.8, Y1 = 27.5, Y2 = 26.3 and Y6 = 26.3; p < 0.001) and negatively correlated with patients' age (rs = −0.120, p = 0.032) and disease duration (rs = −0.103, p = 0.041). Multivariable regression analyses revealed that lower absolute DI scores and larger DI score loss over time were associated with higher probability of EDSS worsening (per −1 point: hazard ratio (HR) = 1.40 (1.16–1.68) and 2.34 (1.27–4.21)), progression independent of relapse activity (PIRA) (HR = 1.49 (1.20–1.85) and 2.22 (1.33–3.31)) and cognitive deterioration (HR = 1.75 (1.35–2.27) and 4.29 (1.26–2.84)) at Y6, but not with time to first relapse. Conclusion: Odour DI is an irreversible marker of neuroaxonal damage, associated with PIRA, cognitive deterioration and EDSS worsening. [ABSTRACT FROM AUTHOR]

Background and purpose: In idiopathic intracranial hypertension (IIH), magnetic resonance imaging (MRI) features are promising diagnostic markers, but the impact of rater experience and the specific referral question is unknown. Methods: From the Vienna Idiopathic Intracranial Hypertension database, patients were included with definitive IIH and routine cranial MRI performed during diagnostic work‐up. Frequencies of partial empty sella (ES), optic nerve sheath distension (ONSD), optic nerve tortuosity (ONT), posterior globe flattening (PGF) and transverse sinus stenosis (TSS) were compared in three settings: (i) real‐world rating, (ii) junior neuroradiologist without special IIH training and (iii) senior neuroradiologist with experience in IIH imaging (gold standard). Results: Magnetic resonance imaging scans of 84 IIH patients (88% female, mean age 33.5 years) were evaluated. By gold standard, ONSD was the most frequent (64.3%) followed by TSS (60.0%), ONT (46.4%), ES (44.4%) and PGF (23.8%). Compared to the gold standard, IIH features were described significantly less frequently in routine MRI reports (ONSD 28.6%, ONT 13.1%, PGF 4.8%, TSS 42.9%, p < 0.01 respectively) except for ES (42.9%, p = 0.9). A specific referral question regarding IIH increased detection rates in routine reports, but rates remained significantly lower than by gold standard. In contrast, a rating by a neuroradiologist without special training produced significantly higher frequencies of ONSD (81.0%, p < 0.01) and ONT (60.7%, p < 0.01) but not of ES (47.6%), PGF (29.8%) and TSS (68.1%). Conclusions: Idiopathic intracranial hypertension MRI features are underestimated in routine MRI reports and partly overcalled by less experienced neuroradiologists, driven by features less well known or methodologically difficult. Reevaluation of MRI scans by an experienced rater (and to a lesser degree a specific referral question) improves diagnostic accuracy. [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]

Background and purpose: COVID‐19 continues to challenge neurologists in counseling persons with multiple sclerosis (pwMS) regarding disease‐modifying treatment (DMT) and vaccination. The objective here was to characterize predictors of COVID‐19 outcome in pwMS. Methods: We included pwMS with polymerase chain reaction‐confirmed COVID‐19 diagnosis from a nationwide population‐based registry. COVID‐19 outcome was classified as either mild or severe. Impact of DMT, specifically anti‐CD20 monoclonal antibodies (anti‐CD20), and vaccination on COVID‐19 outcome was determined by multivariate models adjusted for a priori risk (determined by a cumulative risk score comprising age, disability, and comorbidities). Results: Of 317 pwMS with COVID‐19 (mean age = 41.8 years [SD = 12.4], 72.9% female, median Expanded Disability Status Scale = 1.5 [range = 0–8.5], 77% on DMT [16% on anti‐CD20]), 92.7% had a mild course and 7.3% a severe course, with 2.2% dying from COVID‐19. Ninety‐seven pwMS (30.6%) were fully vaccinated. After a median 5 months from vaccination to SARS‐CoV‐2 infection (range = 1–9), severe COVID‐19 occurred in 2.1% of fully vaccinated pwMS compared to 9.5% in unvaccinated pwMS (p = 0.018). A priori risk robustly predicted COVID‐19 severity (R2 = 0.605, p < 0.001). Adjusting for a priori risk, anti‐CD20 treatment was associated with increased COVID‐19 severity (odds ratio [OR] = 3.3, R2 = 0.113, p = 0.003), but exposure to any other DMT was not. Fully vaccinated pwMS showed a significantly decreased risk for severe COVID‐19 (OR = 0.21, R2 = 0.144, p < 0.001). Conclusions: In a population‐based MS cohort, COVID‐19 course is primarily predicted by a priori risk (depending on age, disability, and comorbidities) explaining about 60% of variance. Anti‐CD20 treatment is associated with a moderately increased risk, whereas reassuringly vaccination provides protection from severe COVID‐19. [ABSTRACT FROM AUTHOR]

Background and purpose: Long‐term outcome after COVID‐19 in patients with multiple sclerosis (pwMS) has scarcely been studied, and controlled data are lacking. The objective of this study was to compare long‐term outcome after COVID‐19 in pwMS to a matched control group of pwMS without COVID‐19. Methods: We included pwMS with polymerase chain reaction‐confirmed diagnosis of COVID‐19 and ≥6 months of follow‐up and, as a control group, pwMS matched 1:1 for age, sex, disability level, and disease‐modifying treatment type. Results: Of 211 pwMS with COVID‐19 (mean age = 42.6 years [SD = 12.2], 69% female, median Expanded Disability Status Scale = 1.5 [range = 0–7.5], 16% anti‐CD20), 90.5% initially had a mild COVID‐19 course. At follow‐up, 70% had recovered completely 3 months (M3) after COVID‐19, 83% after 6 months (M6), and 94% after 12 months (M12). Mild initial COVID‐19 course was the only significant predictor of complete recovery (odds ratio [OR] = 10.5, p < 0.001). The most frequent residual symptoms were fatigue (M3: 18.5%, M6: 13.7%, M12: 7.3%), hyposmia (M3: 13.7%, M6: 5.2%, M12: 1.7%), and dyspnea (M3: 7.1%, M6: 6.6%, M12: 2.8%). Compared to matched controls, fatigue, hyposmia, and dyspnea were significantly more frequent at M3 and still slightly more frequent at M6, whereas there was no difference at M12. pwMS with COVID‐19 had neither a significantly increased risk for relapses (OR = 1.1, p = 0.70) nor disability worsening (OR = 0.96, p = 0.60). Conclusions: Long‐term outcome of COVID‐19 is favorable in a large majority of pwMS, with only a small proportion of patients suffering from persistent symptoms usually resolving after 3–6 months. COVID‐19 is not associated with increased risk of relapse or disability. [ABSTRACT FROM AUTHOR]