The 18th edition of the post-European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) meeting was held on 17-18 October 2025 in Madrid, bringing together Spanish neurologists specialising in multiple sclerosis (MS), who presented the most relevant advances discussed at the ECTRIMS congress held a few days earlier in Barcelona. The aim of the meeting was to summarise the latest developments in the pathogenesis, new diagnostic criteria and biomarkers of MS. This article is the first of a two-part series (I and II) that reviews recent data on cell trafficking into the central nervous system, highlighting the functional heterogeneity of the brain endothelium, the molecular mechanisms regulating leukocyte infiltration and the differential role of macrophages and resident microglia in tissue damage and chronic inflammation. The evidence supporting the role of Epstein-Barr virus as a necessary risk factor in MS is presented, together with the therapeutic and preventive implications from studies of antiviral therapies, cell-based therapies and vaccines. Regarding diagnosis, the new criteria for neuromyelitis optica spectrum disorders are addressed, with particular attention to the molecular heterogeneity of double-seronegative forms, as well as the update of the magnetic resonance imaging (MRI) guidelines following the 2024 revision of the McDonald criteria. Advances in the neuroimaging of chronic active inflammation, quantitative spinal cord imaging and the concept of spinal cord reserve are highlighted. The growing role of artificial intelligence applied to MRI for the early prediction of progression and treatment response is also reviewed. Finally, advances in remyelination mechanisms and in biomarkers are presented, underscoring the value of multimodal and longitudinal approaches for prognostic stratification and treatment monitoring. Overall, the data reviewed reflect a change into a more integrated and predictive understanding of MS, with direct implications for early diagnosis, treatment personalisation and the design of future clinical trials.

The 18th edition of the post-European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) meeting was held on 17-18 October 2025 in Madrid, bringing together Spanish neurologists specialising in multiple sclerosis (MS), who presented the most relevant advances discussed at the ECTRIMS congress held a few days earlier in Barcelona. The aim of this edition was to present the latest developments in MS regarding the update of diagnostic criteria, advanced neuroimaging techniques, the role of Epstein-Barr virus, remyelination mechanisms and biomarkers. In the therapeutic field, emerging treatments were addressed, such as new monoclonal antibodies and chimeric antigen receptor T cells (CAR-T), the management of elderly patients and the risks associated with high-efficacy therapies. This article is the second of a two-part series (I and II). The article reviews recent data on disease progression and on the concept of progression independent of relapse activity (PIRA), including the definition, among those published, that leads to balanced incidence and persistence in PIRA rates. Certain neuropathological and imaging aspects are reviewed, and, with regard to serum biomarkers, it is emphasised that neurofilament light chain (NfL) is a marker of acute damage that is not specific to MS, and that the challenge lies in establishing a value that differentiates it from other diseases. It is also discussed whether the low sensitivity of NfL for predicting progression lies in the z-score used in clinical practice, and the usefulness of glial fibrillary acidic protein (GFAP) in combination with NfL to refine the assessment of chronic progressive damage. The importance of age in MS is indisputable. The elderly patient with MS has a greater number of comorbidities and is more vulnerable to certain treatments. Menopause is a normal but expected physiological transition of female ageing that may trigger or aggravate certain health problems, and whose symptoms should not be confused with worsening of the disease. As for cognitive impairment in MS, the latest developments and expert opinions that could help improve its identification and monitoring are summarised. Much of this part II article focuses on summarising the key advances in emerging therapies and treatment prospects in related diseases, without overlooking the risks associated with very high-efficacy therapies and the possible risk-prevention strategies. Finally, as important findings that translate into clinical practice, the notable improvement in diagnosis with the new 2024 McDonald criteria stands out, despite the barriers to accessing paraclinical tests in certain populations. Overall, the data reviewed, together with those gathered in part I, reflect the research effort to advance the understanding of the disease from multiple complementary perspectives, which is transforming the care of patients with MS.