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Background: COVID-19 vaccines have been recommended to people with multiple sclerosis (pwMS) and, to ensure durable immunity, a third booster dose has been administered in several countries. Data about potential risks associated with the third booster dose in pwMS, such as vaccine-triggered disease exacerbations, are still scarce., Objective: To investigate whether the administration of a third booster dose of mRNA COVID-19 vaccines was associated with an increased risk of short-term disease reactivation in a large cohort of pwMS., Methods: We retrospectively selected 1265 pwMS who received a third booster dose of an mRNA COVID-19 vaccine. Demographic and clinical data were collected, including the presence, number and characteristics of relapses in the 60 days prior to and after the third booster dose., Results: In the selected cohort, the relapse rate in the two months after administration of the third booster dose of mRNA COVID-19 vaccines did not increase when compared with the prior two months. Indeed, the percentage of pwMS experiencing relapses in the 60 days following the administration of the third booster dose was 2.1%, similar to the percentage recorded in 60 days prior to vaccination, which was 1.9%., Conclusions: The third booster dose of mRNA COVID-19 vaccines appeared to be safe for pwMS., (© 2023. The Author(s).)

Upper limb function is one of the most affected domains in people with multiple sclerosis (PwMS), as self-reported by 50% of patients. Heterogeneous results have been found about the correlation between objective and subjective upper limb function. The aim of the present study is to perform a systematic review and meta-analysis of studies presenting data on the strength of association between the gold standard for 9-Hole Peg Test scores and Patient-Reported Outcome Measures (PROMs) of manual ability. Primary research studies including assessments of 9-Hole Peg Test scores and Patient-Reported Outcome Measures were searched in Scopus, Web of Science, and PubMed. Meta analytical calculations were performed using a random-effects model. We retrieved n = 27 studies including n = 75 distinct effect sizes (N of subjects = 3263). The central tendency analysis showed a strong correlation between 9-HPT scores and PROMs (r = 0.51, 95% CI [0.44, 0.58]). Moderator analysis showed the effect size to be significantly larger in studies with a mean or median EDSS level indicating severe disability. The publication bias hypothesis was not supported; instead, we noted that studies based on larger samples also tend to report stronger effect sizes. Results of the study indicate that the correlation between 9-HPT and PROMs is strong, although the constructs measured by these instrument does not fully overlap. The correlation between 9-HPT and PROMs was stronger in larger studies and when samples include a sizeable subgroup of PwMS with severe disability, pointing out the importance of sample diversity., (© 2023. The Author(s).)

Background: Patients with multiple sclerosis (MS) often receive disease-modifying therapies (DMTs) that can expose them to reactivation of potential occult hepatitis B virus (HBV) infection (pOBI). We aimed to evaluate the MS Centers behavior regarding HBV screening and prophylaxis in a large cohort of MS patients receiving anti-CD20 or cladribine., Methods: Retrospective, multicentric study recruiting Italian MS patients treated with rituximab, ocrelizumab and cladribine., Results: We included 931 MS patients from 15 centers. All but 38 patients performed a complete HBV screening. Patients' age > 50 years was significantly associated with no history of vaccination and HBsAb titres < 100 mIU at baseline (p < 0.001). No significant correlation was found between post-vaccination HBsAb titres and type of treatment (p = 0.5), pre-or post-therapy vaccination (p = 0.2) and number of previous DMTs (p = 0.2). Among pOBI patients (n = 53), 21 received antiviral prophylaxis, while only 13 had HBV DNA monitoring and 19 patients neither monitored HBV DNA nor received prophylaxis., Conclusions: Baseline HBV screening in patients receiving anti-CD20 and cladribine is a consolidated practice. Nonetheless, HBV vaccination coverage is still lacking in such population and age is a significant factor associated with low HBV protection. Rituximab, ocrelizumab and cladribine did not impair HBV vaccine response. Almost 35% of pOBI patients fail to receive HBVr prevention. Management of HBV prophylaxis could be improved in MS patients and further prospective studies are needed to assess the effectiveness of prophylactic strategies in such patients., (© 2022. The Author(s).)

Background: Natalizumab (NTZ) is an effective treatment for relapsing-remitting multiple sclerosis (RRMS). However, patients and physicians may consider discontinuing NTZ therapy due to safety or efficacy issues. The aim of our study was to evaluate the NTZ discontinuation rate and reasons of discontinuation in a large Italian population of RRMS patients., Materials and Methods: The data were extracted from the Italian MS registry in May 2018 and were collected from 51,845 patients in 69 Italian multiple sclerosis centers. MS patients with at least one NTZ infusion in the period between June 1st 2012 to May 15th 2018 were included. Discontinuation rates at each time point were calculated. Reasons for NTZ discontinuation were classified as "lack of efficacy", "progressive multifocal leukoencephalopathy (PML) risk" or "other"., Results: Out of 51,845, 5151 patients, 3019 (58.6%) females, with a mean age of 43.6 ± 10.1 years (median 40), were analyzed. Out of 2037 (39.5%) who discontinued NTZ, a significantly higher percentage suspended NTZ because of PML risk compared to lack of efficacy [1682 (32.7% of 5151) vs 221 (4.3%), p < 0.001]; other reasons were identified for 99 (1.9%) patients. Patients discontinuing treatment were older, had longer disease duration and worse EDSS at the time of NTZ initiation and at last follow-up on NTZ treatment. The JCV index and EDSS at baseline were predictors for stopping therapy (HR 2.94, 95% CI 1.22-4.75; p = 0.02; HR 1.36, 95% CI 1.18-5.41; p = 0.04)., Conclusions: Roughly 60% of MS patients stayed on NTZ treatment during the observation period. For those patients in whom NTZ discontinuation was required, it was mainly due to PML concerns., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

In this independent, multicenter, retrospective study, we investigated the short-term persistence to treatment with first-line self-injectable or oral disease-modifying treatments (DMTs) in patients with relapsing-remitting multiple sclerosis. Data of patients regularly attending 21 Italian MS Centres who started a self-injectable or an oral DMT in 2015 were collected to: (1) estimate the proportion of patients discontinuing the treatment; (3) explore reasons for discontinuation; (3) identify baseline predictors of treatment discontinuation over a follow-up period of 12 months. We analyzed data of 1832 consecutive patients (1289 women, 543 men); 374 (20.4%) of them discontinued the prescribed DMT after a median time of 6 months (range 3 days to 11.5 months) due to poor tolerability (n = 163; 43.6%), disease activity (n = 95; 25.4%), adverse events (n = 64; 17.1%), convenience (i.e. availability of new drug formulations) and pregnancy planning (n = 21; 1.1%). Although the proportion of discontinuers was higher with self-injectable (n = 107; 22.9%) than with oral DMT (n = 215; 16.4%), the Cox regression model revealed no significant between-group difference (p = 0.12). Female sex [hazard ratio (HR) = 1.39, p = 0.01] and previous exposure to ≥ 3 DMTs (HR = 1.71, p = 0.009) were two independent risk factors for treatment discontinuation, regardless of prescribed DMTs. Our study confirms that persistence to treatment represents a clinical challenge, irrespective of the route of administration.

Background: Pain is a common and heterogeneous complication of multiple sclerosis (MS). In this multicenter, cross sectional study, we aimed at investigating the prevalence of pain in MS using highly specific criteria for distinguishing the different types of pain., Materials and Methods: After a structured interview, in patients with pain, clinical examination and DN4 questionnaire were used for distinguishing neuropathic and nociceptive pain. In subjects with neuropathic pain, the Neuropathic Pain Symptom Inventory was used for differentiating neuropathic pain symptoms., Results: We enrolled 1249 participants (832 F, 417 M, mean age 33.9 years, mean disease duration 8 years, mean EDSS 3.2); based on clinical evaluation and DN4 score 429 patients (34.34%) were classified with pain (470 pain syndromes): 286 nociceptive pain syndromes and 184 neuropathic pain syndromes. Multivariate analysis showed that pain was associated with age, gender and disease severity and that neuropathic pain was distinctly associated with EDSS., Conclusions: Our study, providing definite information on the prevalence, characteristics and variables associated with neuropathic pain due to MS, shows that a more severe disease course is associated with a higher risk of neuropathic pain. Our findings might, therefore, provide a basis for improving the clinical management of this common MS complication.

The analysis of paired cerebrospinal fluid (CSF) and serum samples with isolectric focusing (IEF) can yield different patterns which can be of aid in the differential diagnosis of central nervous system (CNS) disorders. Rarely, a single CSF-restricted IgG band, which is not included within these patterns, can be detected in association with inflammatory disorders, multiple sclerosis (MS) above all. However, the diagnostic meaning of this abnormality is still uncertain. The main aim of our multicenter study was to establish the frequency and disease associations of single CSF IgG bands. Differences in the CSF profiles between MS and other diseases, and the follow-up patterns were also evaluated. Medical records of patients who underwent CSF analysis, which included IEF, over a 11.5-year period were retrospectively scrutinized at the participating centers, which used similar IEF techniques. One hundred and fifty-one of 9422 CSF reports (1.6%) showed single CSF-restricted IgG bands. Of the 129 patients with a definite diagnosis, 58.2% had CNS inflammatory-demyelinating diseases (the most frequent being MS: 21.7%), 6.2% tumours, 5.4% inflammatory peripheral nervous system diseases and 30.2% miscellaneous diseases. At follow-up, 3 out of the 10 patients with a repeated CSF analysis had developed an oligoclonal band pattern. Our findings indicate that single CSF IgG bands tend to associate with diseases characterized by the involvement of intrathecal humoral immune responses, and strongly support the notion that this abnormality should be regularly reported, thus alerting clinicians of possible inflammatory disorders of the CNS.

The aim of the study was to identify the main factors that impact mobility impairment in multiple sclerosis (MS) patients in Italy. Clinicians from a large number of Italian MS centers took part in a Delphi process aimed at obtaining consensus statements among the participants. Large consensus was obtained for statements grouped under the following main MS themes: identification of the most useful scales to evaluate mobility, integration of objective evaluation with patient perceptions, impact of walking impairment on daily life, management of the disabled patient using a rehabilitative and pharmacological approach. The consensus statements developed by a large number of experts may be used as a practical reference tool to help physicians treat MS patients with motor impairment.