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Several studies have shown the efficacy of rituximab (RTX) in preventing relapses in patients suffering from Neuromyelitis Optica spectrum disorder (NMSOD) and have explored different therapeutic schemes. Given the extreme inter-individual variability of the disease course, there is the need to identify biomarkers to tailor the retreatment schedule and dosage. This review aimed to identify the most useful biomarker to guide reinfusion and, in turn, the optimal retreatment schedule of RTX for NMSOD.The literature search was conducted in the Web of Science, Scopus and Pubmed electronic databases. We limited document type to articles written in English and published up to 28 February 2022. Inclusion criteria were: (i) Patients affected by NMSOD and treated with RTX, (ii) followed up for at least one year and for whom Annualized Relapse rate (ARR) was collected over a period of at least 12 months before and after therapy initiation and (iii) induction protocols consisting of 375 mg / m2 / week for four weeks or 1000 mg infused once or twice two weeks apart. Collected information was: first authors' name, publication year, study design, sample size, sex, age, percentage of patients positive for antibodies to aquaporin 4 (AQP4-IgG), maintenance regimen, primary outcome, mean ARR pre-therapy and mean ARR post-therapy initiation, percentage of relapse-free patients. The primary outcome that we considered was the ARR reduction. Further, we considered the number of relapses that occurred when B cells and memory B cells were under the chosen threshold and the percentage of relapse-free patients when available.Among 31 potentially eligible studies, 9 fulfilled the inclusion criteria. ARR reduction was not comparable between studies. The studies that monitored CD19+ and CD27+ cell kinetics showed a higher number of relapses when CD19+ lymphocyte count was below the threshold compared to the number of relapses that occurred when CD27+ cell count was below the threshold. Further, a higher percentage of patients achieved the relapse-free condition with a reinfusion schedule when CD27+ reached 0, 05% of peripheral blood mononuclear cells (PBMCs) compared to the reinfusion when CD19+ reached 0, 1% of PBMCs.To date, the optimal retreatment schedule for RTX in NMOSD has not yet been determined. However, the presented findings suggest that CD27+ B cells might be a reliable biomarker to guide retreatment in AQP4-IgG positive patients, at least in the first six months from the infusion. Further effort is needed to identify those factors influencing anti-CD20 therapy effectiveness to tailor dosage and treatment schedule to achieve the most favourable risk/benefit ratio.

Background: Several observational studies have shown an association between low circulating levels of 25-hydroxy- vitamin D (25(OH)D) and an increase in inflammatory activity in Multiple Sclerosis (MS). Among its immunomodulatory functions, 25(OH)D suppresses proliferation and immunoglobulin production of B cells. 25(OH)D supplementation has been associated with better radiological outcomes in MS patients treated with interferon (IFN)-B, glatiramer acetate, fingolimod, natalizumab and rituximab. Our study is aimed at analyzing the association of 25(OH)D serum levels and supplementation with B cell kinetics and clinical-radiological outcomes of people with MS treated with ocrelizumab. Methods: We have retrospectively collected clinical and radiological data from 136 MS patients who have been treated with ocrelizumab, have undergone at least two treatment cycles and for whom data on serum 25(OH)D levels and intake were available. The patients were divided into three groups according to baseline 25(OH)D serum levels: deficient (≤19,9 ng/ml), insufficient (20-29,9 ng/ml), and normal range 25(OH)D (>30 ng/ml). According to 25(OH)D intake, we divided our population into users and non-users. To explore B cell kinetics at six- and twelve-month follow-ups, the patients were divided into two groups: with fast repopulation (FR) and slow repopulation rate (SR), based on the reappearance or non- appearance of CD19 at each time point. Results: When considering the entire population, the mean 25(OH)D serum level (sd) was 26.27 ng/ml (14.15). 43 (31,62%) patients were classified as deficient, 52 (38,24%) were classified as insufficient, and 41 (30,14%) showed 25(OH)D serum levels within the normal range. 60.29% (82/136) of the patients were classified as users, and 39.70% (54/136) as non-users. Over the eighteen-month treatment period, we observed a significant difference between the 25(OH)D users and the non-users as concerns the number of scans with at least one new/enlarging T2 lesion (2% vs 15.38%, respectively; p= 0.025). In the multinomial regression model, 25(OH)D deficiency (serum levels ≤19,9 ng/ml) was significantly associated with a higher likelihood of disease activity during a follow-up of eighteen months (p=0.029, RRR=4.84, Confidence Interval (CI) 1.17 - 20.01). After six months, there were 30/136 FR patients (22,05%), whereas only 22/136 (16,17%) showed early B cell reappearance at twelve month follow up. 86.66% of the patients in the FR group showed 25(OH)D levels lower than 30 ng/ml (25(OH)D deficiency or insufficiency), whereas only 65.09% of the SR patients presented vitamin D levels lower than 30 ng/ml (p= 0.024). In the logistic regression model, 25(OH)D serum levels below 30 ng/ml were associated with a higher likelihood of early B cell reappearance at six month follow up (p= 0.042). Conclusions: 25(OH)D supplementation and serum levels might be associated with B cell kinetics and radiological activity of patients with MS treated with ocrelizumab.

Background: Clinicians struggle to timely diagnose secondary-progressive multiple sclerosis (SP-MS), with a ‘transition phase’ period of diagnostic uncertainty. We aimed at defining clinical markers predicting evolution to SP-MS. Methods:: We reviewed 210 newly diagnosed MS patients experiencing at least one confirmed disability worsening (CDW). CDWs were classified as disability worsening either due to incomplete recovery following relapse (r-CDW), or independent of relapse activity (nr-CDW). Logistic regression and Cox regression models were used to evaluate variables at CDW associated with SP-MS diagnosis. Results: On CDW, higher EDSS (OR: 2.73, p=0.002) and nr-CDW (OR: 2.63, p=0.03) were associated with conversion to SP-MS over the follow-up. In addition, the risk of SP-MS was higher in patients with EDSS>3.0 at CDW (HR: 2.26, p

Background The Dress picture recently has become a hot topic on the Internet, prompting a debate whether it was black and blue, or white and gold. Objective To investigate The Dress color perception in both multiple sclerosis (MS) patients, characterized by frequent visual system impairment with ensuing color vision effects, and general population. Methods We developed a questionnaire to record demographics, clinical features, and The Dress color perception, posted on general and MS-specific social networks. Results No statistically significant differences were observed in The Dress color perception between MS patients ( n =103) and general population ( n =441). Furthermore, white and gold color perception was positively associated with aging in the general population ( p =0.04), whereas negatively associated with progressive course ( p =0.03) and longer disease duration ( p Conclusion The Dress black and blue or white and gold perception might be due to aging in the general population, whereas black and blue perception, despite of aging, might suggest a specific effect of the MS burden (i.e. disease duration and progression) on the visual structures specifically involved in the white and gold perception.