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<jats:p> The 2022 ECTRIMS lecture focused on pediatric-onset multiple sclerosis (POMS), in recognition of the pivotal importance of prompt recognition and treatment of children and youth diagnosed with multiple sclerosis (MS), enabled over the past decade by the formal inclusion of pediatric patients in the McDonald diagnostic criteria. Epidemiologic, genetic and immunologic research has supported the concept that MS is a single disease across the age span and that clues to the inciting and early facets of MS pathobiology might be uniquely discerned through study of the youngest MS patients. Pediatric trials of pharmaceutical agents approved in adult-onset MS are emerging, although innovative study designs, alignment of regulatory agency requirements for trial design, family-centric models for study visits and emphasis on long-term safety and tolerability are essential. Evidence of safety and efficacy of key therapies is key if POMS patients are to be availed of the full armamentarium of MS therapeutic options. Finally, the rarity of POMS necessitates an international community effort to advance care and research. Such collaborations have been facilitated through the International Pediatric Multiple Sclerosis Group, Multiple Sclerosis International Federation, and by national multiple sclerosis societies. International efforts and priorities for the next decade will be highlighted. </jats:p>

<jats:sec><jats:title>Background:</jats:title><jats:p> With the new highly active drugs available for people with multiple sclerosis (pwMS), vaccination becomes an essential part of the risk management strategy </jats:p></jats:sec><jats:sec><jats:title>Objective:</jats:title><jats:p> To develop a European evidence-based consensus for the vaccination strategy of pwMS who are candidates for disease-modifying therapies (DMTs). </jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p> This work was conducted by a multidisciplinary working group using formal consensus methodology. Clinical questions (defined as population, interventions, and outcomes) considered all authorized DMTs and vaccines. A systematic literature search was conducted and quality of evidence was defined according to the Oxford Centre for Evidence-Based Medicine Levels of Evidence. The recommendations were formulated based on the quality of evidence and the risk–benefit balance. </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> Seven questions, encompassing vaccine safety, vaccine effectiveness, global vaccination strategy and vaccination in sub-populations (pediatric, pregnant women, elderly and international travelers) were considered. A narrative description of the evidence considering published studies, guidelines, and position statements is presented. A total of 53 recommendations were agreed by the working group after three rounds of consensus. </jats:p></jats:sec><jats:sec><jats:title>Conclusion:</jats:title><jats:p> This first European consensus on vaccination in pwMS proposes the best vaccination strategy according to current evidence and expert knowledge, with the goal of homogenizing the immunization practices in pwMS. </jats:p></jats:sec>

<jats:sec><jats:title>Introduction:</jats:title><jats:p> Natalizumab is associated with a risk of progressive multifocal leukoencephalopathy (PML) in multiple sclerosis (MS) patients infected with John Cunningham virus (JCV). Ocrelizumab has demonstrated efficacy to treat MS; however, its safety in patients previously treated with natalizumab is unclear. </jats:p></jats:sec><jats:sec><jats:title>Objective:</jats:title><jats:p> To evaluate the safety and efficacy of ocrelizumab in patients with relapsing MS (RMS) previously treated with natalizumab. </jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p> Clinically and radiographically stable RMS patients, ages 18–65 treated with natalizumab for ⩾ 12 months, were enrolled in the study and initiated ocrelizumab 4–6 weeks after their final dose of natalizumab. Relapse assessment, expanded disability status scale, and brain magnetic resonance imaging (MRI) were performed prior to starting ocrelizumab and at months 3, 6, 9, and 12. </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> Forty-three patients were enrolled, and 41 (95%) completed the study. Two patients had a relapse while on ocrelizumab, one at month 9 and the other at month 12, without changes on brain MRI. Two additional patients had new brain MRI lesions detected at month 3, with no new symptoms. Thirteen serious adverse events (SAEs) were recorded, four of which were considered possibly related to ocrelizumab. </jats:p></jats:sec><jats:sec><jats:title>Conclusion:</jats:title><jats:p> Overall, our study indicates clinical and MRI stability for most patients transitioning from natalizumab to ocrelizumab. </jats:p></jats:sec><jats:sec><jats:title>ClinicalTrials.gov Identifier:</jats:title><jats:p> NCT03157830 </jats:p></jats:sec>

<jats:sec><jats:title>Objective:</jats:title><jats:p> There is some evidence implicating diet in the development of inflammatory diseases. We aimed to study the influence of dietary habits on the risk of developing multiple sclerosis (MS). </jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p> We used a population-based case–control study recruiting incident cases of MS (1953 cases, 3557 controls). Subjects with different dietary habits 5 years prior to MS diagnosis were compared regarding MS risk by calculating odds ratios (OR) with 95% confidence intervals (CI) using logistic regression models. Adjustment was made for a large number of environmental and lifestyle habits, including ancestry, smoking, alcohol consumption, body mass index, physical activity, and sun exposure habits. </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> Mediterranean diet was associated with lower risk of developing MS (adjusted OR = 0.54, 95% CI: 0.34–0.86, p = 0.009), compared with Western-style diet. There was no significant association between vegetarian/vegan diet and MS risk (adjusted OR = 0.96, 95% CI: 0.75–1.24, p = 0.976), nor between diet with low glycemic index and MS risk (adjusted OR = 0.93, 95% CI: 0.60–1.42, p = 0.518). </jats:p></jats:sec><jats:sec><jats:title>Conclusions:</jats:title><jats:p> Mediterranean diet may exert a protective influence regarding the risk of subsequently developing MS compared with Western-style diet. </jats:p></jats:sec>

<jats:sec><jats:title>Background:</jats:title><jats:p> The potential therapeutic benefit of intravenous immunoglobulins (IVIGs) for acute attacks of myelin oligodendrocyte glycoprotein antibody disease (MOGAD) is unknown. </jats:p></jats:sec><jats:sec><jats:title>Objective:</jats:title><jats:p> The objective was to describe the outcomes of IVIG treatment for acute MOGAD attacks. </jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p> A retrospective observational study involving seven tertiary neuroimmunology centers. Data collection included patients’ demographics, Expanded Disability Status Scale (EDSS), and visual acuity (VA) before the attack, at the nadir of the attack before IVIG treatment, and at follow-up visits ⩾3 months after treatment. </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> Thirty-nine patients were included, of which 21 (53.8%) were female. The median age was 23 years (range 5–74 years), and the median disease duration was 4 months (range 0–93 months). The most common type of attack treated with IVIG was isolated optic neuritis (ON) (unilateral n = 14, bilateral n = 5, associated with transverse myelitis (TM), n = 1), followed by acute disseminated encephalomyelitis (ADEM) ( n = 8), multifocal ( n = 7), TM ( n = 3), brainstem ( n = 1), and other encephalitis ( n = 1). A significant improvement in both the EDSS and VA measures was observed at follow-up compared to the time of IVIG treatment initiation ( p &lt; 0.0001 for both outcome measures). </jats:p></jats:sec><jats:sec><jats:title>Conclusion:</jats:title><jats:p> IVIG may be an effective treatment option for acute MOGAD attacks. Further prospective studies are warranted to validate our results. </jats:p></jats:sec>

<jats:sec><jats:title>Background:</jats:title><jats:p> We aimed to assess the frequency of new asymptomatic lesions on brain and spinal imaging (magnetic resonance imaging (MRI)) and their association with subsequent relapses in a large cohort of neuromyelitis optica spectrum disorder (NMOSD) patients in Argentina. </jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p> We retrospectively reviewed 675 MRI (225 performed during an attack and 450 during the relapse-free period (performed at least 3 months from the last attack)) of NMOSD patients who had at least 2 years of clinical and MRI follow-up since disease onset. Kaplan–Meier (KM) curves were used for depicting time from remission MRI to subsequent relapse. </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> We included 135 NMOSD patients (64.4% were aquaporin-4-immunoglobulin G (AQP4-IgG)-positive). We found that 26 (19.26%) and 66 (48.88%) of patients experienced at least one new asymptomatic MRI lesion during both the relapse-free period and attacks, respectively. The most frequent asymptomatic MRI lesions were optic nerves followed by short-segment myelitis during the relapse-free period and attacks. KM curves did not show differences in the time taken to develop a new relapse. </jats:p></jats:sec><jats:sec><jats:title>Conclusion:</jats:title><jats:p> Our findings showed that new asymptomatic lesions are relatively frequent. However, the presence of new asymptomatic MRI lesions during the relapse-free period and at relapses was not associated with a shorter time to developing subsequent relapses. </jats:p></jats:sec>

<jats:sec><jats:title>Background:</jats:title><jats:p> Pseudocystic inflammatory demyelinating lesions (PIDLs) are poorly described in MS and might represent a diagnostic challenge. </jats:p></jats:sec><jats:sec><jats:title>Objectives:</jats:title><jats:p> We described the clinical, radiological, pathological, and follow-up characteristics of 13 PIDL in 9 MS patients. </jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p> We constituted a single-center retrospective case series of PIDLs in MS, defined on MRI as expansive cyst-like lesions, with a fluid-signal content, and a diameter of 1 cm or more. </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> PIDL often occurred at first event (56%), were often asymptomatic (69%), and encircled by a hypo-T2 diffusion-restricted rim and a thin ring-like gadolinium enhancement (100%) on magnetic resonance imaging (MRI). Associated typical MS lesions were constant. Biopsies from two PIDLs displayed classical features of active MS, except for unusual edema. </jats:p></jats:sec><jats:sec><jats:title>Conclusion:</jats:title><jats:p> PIDLs are clinically unremarkable and associated with a good outcome. Their easily recognizable MRI features could help avoid biopsy. </jats:p></jats:sec>

<jats:sec><jats:title>Background:</jats:title><jats:p> The role of vaccine-mediated inflammation in exacerbating multiple sclerosis (MS) is a matter of debate. </jats:p></jats:sec><jats:sec><jats:title>Objective:</jats:title><jats:p> In this cross-sectional study, we compared the cerebrospinal fluid (CSF) inflammation associated with MS relapses or anti-COVID-19 mRNA vaccinations in relapsing-remitting multiple sclerosis (RRMS). </jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p> We dosed CSF cytokines in 97 unvaccinated RRMS patients with clinical relapse within the last 100 days. In addition, we enrolled 29 stable RRMS and 24 control patients receiving COVID-19 vaccine within the last 100 days. </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> In RRMS patients, a negative association was found between relapse distance and the CSF concentrations of the pro-inflammatory cytokines interleukin (IL)-2 (beta = −0.265, p = 0.016), IL-6 (beta = −0.284, p = 0.01), and IL-17 (beta = −0.224, p = 0.044). Conversely, vaccine distance positively correlated with a different set of cytokines including IL-12 (beta = 0.576, p = 0.002), IL-13 (beta = 0.432, p = 0.027), and IL-1ra (beta = 0.387, p = 0.05). These associations were significant also considering other clinical characteristics. No significant associations emerged between vaccine distance and CSF molecules in the control group. </jats:p></jats:sec><jats:sec><jats:title>Conclusion:</jats:title><jats:p> Vaccine for COVID-19 induces a central inflammatory response in RRMS patients that is qualitatively different from that associated with disease relapse. </jats:p></jats:sec>