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Introduction: Environmental factors appear to play an important role in the development and course of Multiple Sclerosis (MS). Seasonal variability in disease activity has been described and it is postulated that it may vary according to geographical area. The aim of this study is to analyse the monthly distribution of activity observed on Magnetic Resonance Imaging (MRI) and to look for a possible relationship with climate in patients with relapsing remitting MS., Material and Methods: Retrospective observational study, carried out in the population of one hospital on the Spanish Mediterranean coast. A total of 238 MRI scans of 51 patients were evaluated. Climatological data were obtained from the Spanish State Meteorological Agency from 2012 to 2016. Activity was defined as contrast-enhancing lesions., Results: The distribution of gadolinium-enhancing lesions was found to be non-uniform across months (p = 0.008). Visual inspection suggests higher activity in July and August. Regarding weather, tropical nights (defined as days with a minimum temperature above 20 °C) were associated with increased risk of MRI activity (OR = 1.06, p = 0.001)., Conclusion: These findings suggest a non-uniform monthly distribution of gadolinium-enhancing lesions and an association between warmer nights and increased MRI activity, pointing to a potential impact of environmental factors on multiple sclerosis activity in neuroimaging., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The assessment of serum neurofilament light chain (sNfL) concentration in multiple sclerosis (MS) is a useful tool for predicting clinical outcomes and assessing treatment response. However, its use in clinical practice is still limited. We aimed to assess how measurement of sNfL influences neurologists' treatment decisions in MS., Methods: We conducted a cross-sectional, web-based study in collaboration with the Spanish Society of Neurology. Neurologists involved in MS care were presented with different simulated case scenarios of patients experiencing either their first demyelinating MS event or a relapsing-remitting MS. The primary outcome was therapeutic inertia (TI), defined as the absence of treatment initiation or intensification despite elevated sNfL levels. Nine cases were included to estimate the TI score (range 0-9, where higher values represented a higher degree of TI)., Results: A total of 116 participants were studied. Mean age (standard deviation-SD) was 41.9 (10.1) years, 53.4 % male. Seventy-eight (67.2 %) were neurologists fully dedicated to the care of demyelinating disorders. Mean (SD) TI score was 3.65 (1.01). Overall, 92.2 % of participants (n = 107) presented TI in at least 2/9 case scenarios. The lack of full dedication to MS care (p = 0.014), preference for taking risks (p = 0.008), and low willingness to adopt evidence-based innovations (p = 0.009) were associated with higher TI scores in the multivariate analysis after adjustment for confounders., Conclusion: TI was a common phenomenon among neurologists managing MS patients when faced with the decision to initiate or escalate treatment based on elevated sNfL levels. Identifying factors associated with this phenomenon may help optimize treatment decisions in MS care., Competing Interests: Declaration of competing interest Gustavo Saposnik received consulting fees from Roche Farma Spain and is supported by the University of Toronto Scientific Merit award. He also receives a modest stipend from the World Stroke Organization as the Editor in Chief of the World Stroke Academy. Enric Monreal reported receiving research grants, travel support, or honoraria for speaking engagements from Almirall, Merck, Roche, Sanofi, Bristol Myers Squibbb, Biogen, Janssen, and Novartis. Jose M García-Domínguez received honoraria as speaker, advisor and researcher from Almirall, Bristol Myers Squibb, Biogen, Janssen, Merck, Novartis, Roche, Teva, and Sanofi. Jose E Meca-Lallana received honoraria as a consultant, chairman and lecturer in meetings and participated in clinical trials and other research projects promoted by Alexion, Biogen, Bristol Myers Squibb, Janssen, Merck, Novartis, Roche, and Sanofi. Lamberto Landete received honoraria for participating in advisory boards and scientific and educational activities from Almirall, Bayer, Biogen, Bristol Myers Squibb, Sanofi, Merck, Novartis, UCB, Roche, and Teva. Virginia Meca-Lallana received consulting and speaking fees from Almirall, Biogen, Genzyme, Janssen, Merck, Novartis, Roche, Terumo, Sanofi, Teva, and Bristol Myers Squibb. Luis Querol received speaker honoraria from Merck, Sanofi, Roche, Biogen, Grifols and CSL Behring; provided expert testimony for Grifols, Johnson & Johnson, Annexon Pharmaceuticals, Sanofi, Novartis, Takeda, and CSL-Behring; and received research funds from Roche, UCB, and Grifols. Eduardo Agüera received speaking honoraria from Roche, Novartis, Merck, Sanofi, and Biogen. Sergio Martínez-Yélamos received honoraria for participating on advisory boards and for collaborations as consultant and scientific communications; they also received research support as well as funding for travel and congress expenses from Roche, Biogen Idec, Novartis, TEVA, Merck, Genzyme, Sanofi, Bayer, Almirall, and Bristol Myers Squibb. Luisa M Villar reported receiving research grants and personal fees from Merck, Roche, Sanofi, Bristol Myers Squibb, Biogen, and Novartis. Ana B Caminero received courses and honoraria for her participation as speaker/meeting moderator/symposia organizer from Alter, Almirall, Bayer, Bial, Biogen, Bristol Myers Squibb, Lilly, Merck, Mylan, Novartis, Roche, Sanofi-Genzyme, Teva, and UCB; and support to attend scientific meetings from Biogen, Bial, Merck-Serono, Novartis, Roche, Sanofi, and Teva. Rocío Gómez-Ballesteros, Elisa Salas, Nicolas Medrano, Elena García-Arcelay, and Jorge Maurino are employees of Roche Farma Spain., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: People with secondary progressive multiple sclerosis (pwSPMS) experience increasing disability, which impacts negatively on their health-related quality of life (HRQoL). Our aims were to assess the impact of secondary progressive multiple sclerosis (SPMS) on functional status and HRQoL and describe the clinical profile in this population., Methods: DISCOVER is an observational, cross-sectional, multicenter study with retrospective data collection in real-world clinical practice in Spain. Sociodemographic and clinical variables, functional and cognitive scales, patient-reported outcomes (PROs), and direct healthcare, and non-healthcare and indirect costs were collected., Results: A total of 297 evaluable pwSPMS with a EDSS score between 3-6.5 participated: 62.3 % were female and 18.9 % had active SPMS. At the study visit, 77 % of them presented an Expanded Disability Scale Score (EDSS) of 6-6.5. Nearly 40 % did not receive any disease-modifying treatment. Regarding the working situation, 61.6 % were inactive due to disability. PROs: 99.3 % showed mobility impairment in EuroQoL-5 Dimensions-5 Levels, and about 60 % reported physical impact on the Multiple Sclerosis Impact Scale-29. Fatigue was present in 76.1 %, and almost 40 % reported anxiety or depression. The Symbol Digit Modalities Test was used to assess cognitive impairment; 80 % of the patients were below the mean score. Participants who presented relapses two years before and had high EDSS scores had a more negative impact on HRQoL. PwSPMS with a negative impact on HRQoL presented a higher cost burden, primarily due to indirect costs., Conclusions: PwSPMS experience a negative impact on their HRQoL, with a high physical impact, fatigue, cognitive impairment, and a high burden of indirect costs., Competing Interests: Declaration of competing interest None, (Copyright © 2024. Published by Elsevier B.V.)

Background: Standardizing health outcomes is challenging in clinical management, but it also holds the potential for creating a healthcare system that is both more effective and efficient. The aim of the present study is to define a standardized set of health outcomes for managing Relapsing-Remitting Multiple Sclerosis (RRMS)., Methods: The project was led and coordinated by a multidisciplinary scientific committee (SC), which included a literature review, a patient-focused group, three nominal group meetings, and two SC meetings., Results: 36 outcome variables were included in the standard set: 24 clinical (including weight, smoking habit, comorbidities, disability, mobility, diagnosis of secondary progressive multiple sclerosis, relapsed-related variables, radiological variables, cognitive status and disease-related symptoms), nine treatment-related (pharmacological and non-pharmacological information), and 3 related to the impact of RRMS on the patient's life (quality of life, pregnancy desire, work-related difficulties). In addition, experts also agreed to collect 10 case-mix variables that may affect but cannot be controlled as part of the management of the condition: 4 sociodemographic (age, sex, race, and employment status) and 6 clinical (height, date of diagnosis and first episode, serological status, early symptoms, and number of relapses pre-diagnosis)., Conclusion: The information provided through the present standard set of outcome variables can improve the management of RRMS and promote patient-centred quality care., Competing Interests: Declaration of competing interest MLG has received fees from the following pharmaceutical companies for his participation in advisory groups, talks, workshops, seminars, conferences, studies or clinical trials: Bayer, Biogen, Teva, Novartis, Sanofi-Genzyme, Almirall, Roche, Bristol Myers Squibb, Merk and Janssen. PCR has served as a speaker for several pharmaceutical companies. ODS reports fees as a study investigator with Pfizer and Bristol Myers Squibb. MB declares relationships with Bristol Myers Squibb, Roche and Biogen. ARA has participated in scientific consultancies and has been a speaker at scientific meetings organized by Merk, Biogen, Novartis, Sanofi, Teva and Bristol Myers Squibb. AMB has no conflicts of interest to disclose. NBR declares relationships with Roche, Merck, Biogen, Sanofi, Janssen and Bristol Myers Squibb. AR serves on scientific advisory boards for Bristol Myers Squibb, Novartis, Sanofi-Genzyme, Synthetic MR, Tensor Medical, Roche, Biogen, and OLEA Medical and has received speaker honoraria from Bayer, Sanofi-Genzyme, Merck-Serono, Teva Pharmaceutical Industries Ltd, Novartis, Roche, Bristol Myers Squibb, and Biogen. AR is also a member of the editorial boards of Neurology and Neuroradiology and the executive committee of MAGNIMS. VML has not declared conflicts of interest. LBP and MC are employees of Outcomes 10, an independent research entity that has received fees from Bristol Myers Squibb for conducting this research. DV and AE are employees and may be shareholders of Bristol Myers Squibb. CO-G has received speaker and consultation fees from Alexion, Biogen Idec, Bristol Myers Squibb, Janssen, Merck, Novartis, Roche, Sanofi-Genzyme and Teva., (Copyright © 2024. Published by Elsevier B.V.)

Background: The increase in available disease modifying therapies (DMTs) for multiple sclerosis has led to greater emphasis on improving treatment sequencing paradigms. This article summarises the opinions from a panel of 25 experts on treatment switching approaches in relapsing multiple sclerosis (RMS)., Methods: A modified Delphi consensus process was carried out to develop clinically relevant statements for aiding treatment decisions in patients with RMS between the 16 th January and the 9 th October 2019. A sub-group of two experts (core group) carried out an extensive review of the literature and formulated 106 statements for the expert panel to evaluate., Results: From a total number of 106 statements that were submitted to the expert panel for critical evaluation, consensus (at least 80% of the panelists agreed) was reached on 99 of them. These statements cover treatment objectives, reasons for DMT switching, suboptimal response criteria, strategies for treatment change and washout periods., Conclusion: The agreed statements provide up-to-date guidance on DMT sequencing for optimal patient management., (Copyright © 2022. Published by Elsevier B.V.)

Background: Primary progressive multiple sclerosis (PPMS) has long been defined by progressive disability accrual in the absence of initial relapses. However, its underlying neurodegenerative process seems to be accompanied by central nervous system inflammation. A new classification defined multiple sclerosis courses according to clinical/radiological activity and progression. We provide further insight into PPMS activity according to this classification and other daily living aspects., Methods: This was a multicentre, prospective, cohort study including 55 adult patients with PPMS according to 2010 McDonald criteria, within ten years from neurologic symptom onset and not receiving disease-modifying therapies during the past six months, who were followed up for 12 months. The primary study endpoint was the percentage of patients with active disease based on clinical relapses and/or magnetic resonance activity. Disability progression, cognitive function, physical/psychological impact, depression symptoms, stigma and employment were secondary endpoints., Results: Eleven (25.6%) patients exhibited multiple sclerosis activity throughout the 12-month study follow-up. Fourteen showed non-active multiple sclerosis without progression, 11 non-active multiple sclerosis with progression, 6 active multiple sclerosis without progression and 4 active multiple sclerosis with progression; one patient with disease activity was not assessable for progression. Cognitive function scores remained unchanged or increased, disease physical impact was maintained and disease psychological impact significantly decreased. The proportion of patients with depression symptoms or stigma remained without significant changes as well as employment outcomes., Conclusion: This study shows that one-fourth of PPMS patients may exhibit disease activity over one year, with disability progression in approximately one-third but without worsening of cognitive function, disease impact, depression, stigma or employment outcomes., (Copyright © 2021. Published by Elsevier B.V.)

Background and Aim: In December 2019, the first cases of SARS-CoV-2 infection were detected in Wuhan. Within two months, it had begun to spread around the world in what became an unprecedented pandemic. Patients with Multiple Sclerosis (MS) in a state of immunosuppression may be considered at risk for complications in the COVID-19 pandemic, although there is increasing evidence postulating a possible protective role of selective immunosuppression. One group of such immunosuppressants used in MS comprises the anti-CD20 monoclonal antibodies (mAbs) ocrelizumab and rituximab. Anti-CD20 mAbs bind to the surface of B cells, causing their depletion. We describe our experience in seven cases of patients with multiple sclerosis who have been affected by SARS-COV-2 (with a clinical/serological diagnosis or PCR diagnosis) and who were being treated with anti-CD20+ monoclonal antibodies., Material and Methods: We review the development of patients during infection as well as the resolution of their clinical picture. We also analyze the serology status against SARS-CoV-2 after resolution of the infection., Results: Although the severity of the clinical pictures was variable, patients' development was good. Not all patients, however, developed antibodies against SARS-CoV-2., Conclusions: Patients treated with anti-CD20+ have adequate resolution of COVID-19 despite the fact that the presence of antibodies against SARS-CoV-2 was not detected in all cases. It is possible that the presence of humoral immunity is not always necessary fora good clinical course of SARS-CoV-2 infection., (Copyright © 2020. Published by Elsevier B.V.)

Alemtuzumab is an anti-CD52 monoclonal antibody approved for the treatment of multiple sclerosis (MS). It produces rapid depletion of T and B lymphocytes, which could predispose to opportunistic infections. We report one patient with MS who develops cytomegalovirus (CMV) primary infection after a third cycle of alemtuzumab, with spontaneous recovery associated with rapid lymphocyte reconstitution., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background and Objective: Fingolimod is a sphingosine 1-phosphate receptor modulator, which sequesters lymphocytes in lymph nodes and prevents them from entering the central nervous system. There have been increasing reports of severe rebounds with tumefactive demyelinatinglesions (TDLs) in patients with multiple sclerosis under fingolimod treatment, as well as following therapy discontinuation. Our objective is to review the clinico-radiological characteristics of patients with TDLs associated with fingolimod., Methods: Retrospective review of medical records of MS patients from our center, who were treated with fingolimod and developed TDLs. We review the literature., Results: We found 5 cases: 4 developed TDLs as rebounds after treatment cessation and 1 under treatment. The 4 rebound cases were women, with a mean age of 34.7 years (SD = 3.6) and a mean disease duration of 10.2 years (SD = 4.1). The mean duration of fingolimod treatment before discontinuation was 36.2 months (SD = 22.4) and the mean time lapse between treatment withdrawal and rebound was 9.75 weeks (SD = 7.4). The total pre-rebound lymphocyte count (cells/mm3) was 482.5 (SD = 325.7) and1017.5 (SD = 364.8) during rebound. The TDL patient under fingolimod was a 36-year-old man who had been on fingolimod for 32 months after switching from glatiramer acetate. TDLs were multiple in 2 cases and solitary in 3. Acute treatment for rebound included high dose steroids (5/5), plasma exchange (3/5) and rituximab (2/5). Treatment after fingolimod included rituximab (2/5), alemtuzumab (2/5) and glatiramer acetate (1/5)., Conclusions: Our study, along with similar reports in literature, highlights the need for close monitoring in patients who plan to switch from fingolimod to other treatments because of the risk of severe rebound. The etiopathogenic association between fingolimod and TDLs is not clear, but given the increasing reports of cases it should be taken into account for treatment selection in patients with this type of lesions., (Copyright © 2018 Elsevier B.V. All rights reserved.)