The XVI Post-ECTRIMS meeting took place in Seville on 20 and 21 October 2023. This meeting was attended by neurologists specialising in multiple sclerosis (MS) from Spain, who shared a summary of the most interesting innovations at the ECTRIMS congress, which had taken place in Milan the previous week. The aim of this article is to summarise new developments related to the pathogenesis, diagnosis and prognosis of MS. The contributions of innate immunity and central nervous system resident cells, including macrophages and microglia in MS pathophysiology and as therapeutic targets were discussed. Compartmentalised intrathecal inflammation was recognised as central to understanding the progression of MS, and the relationship between inflammatory infiltrates and disease progression was highlighted. Perspectives in demyelinating pathologies were reviewed, focusing on neuromyelitis optica and myelin oligodendrocyte glycoprotein antibody-associated disease, highlighting their pathophysiological and diagnostic differences compared to MS. Advances in neuroimaging were also discussed, and especially the analysis of active chronic lesions, such as paramagnetic rim lesions. In the absence of clinical improvements in trials of remyelinating treatments, methodological strategies to optimise the design of future studies were proposed. Breakthroughs in detecting the prodromal phase of MS, the use of biomarkers in body fluids to assess activity, progression and treatment response, and research on progression independent of flares were addressed. The need to define criteria for radiologically isolated syndrome and to clarify the concept was also discussed.
BACKGROUND: XVI Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2023 (I).
La XVI edición de la reunión Post-ECTRIMS se celebró los días 20 y 21 de octubre de 2023 en Sevilla. Este encuentro reunió a neurólogos especialistas en esclerosis múltiple (EM) de España, quienes compartieron un resumen de las innovaciones más destacables del congreso ECTRIMS, acontecido en Milán la semana anterior. El objetivo de este artículo es sintetizar las novedades relativas a la patogenia, el diagnóstico y el pronóstico de la EM. Se destacaron las contribuciones de la inmunidad innata y las células residentes del sistema nervioso central, incluyendo macrófagos y microglía, en la patofisiología de la EM y como objetivos terapéuticos. La inflamación intratecal compartimentada se reconoció como fundamental para entender la progresión de la EM, y destaca la relación entre infiltrados inflamatorios y la evolución de la enfermedad. Se revisaron perspectivas en patologías desmielinizantes, enfocadas en la neuromielitis óptica y la enfermedad asociada a anticuerpos contra la glucoproteína de mielina de oligodendrocitos, subrayando sus distinciones patofisiológicas y diagnósticas con la EM. También se abordaron los avances en neuroimagen, especialmente en el análisis de las lesiones crónicas activas, como las lesiones con borde paramagnético. Ante la ausencia de mejoras clínicas en ensayos de tratamientos remielinizantes, se propusieron estrategias metodológicas para optimizar el diseño de futuros estudios. Se abordaron los avances en la detección de la fase prodrómica de la EM, el uso de biomarcadores en fluidos corporales para evaluar la actividad, la progresión y la respuesta al tratamiento, y la investigación sobre la progresión independiente de la actividad de brote. Además, se debatió sobre la necesidad de definir criterios para el síndrome radiológico aislado o precisar su concepto.

Background and Objectives: Multiple sclerosis (MS) is a chronic neurodegenerative disease often linked with systemic conditions such as periodontal diseases (PDs). This systematic review aims to explore the association between inflammatory markers in saliva and PDs in MS patients, assessing the use of saliva as a non-invasive tool to monitor disease progression. Materials and Methods: 82 publications were examined after a thorough search of scholarly databases to determine whether inflammatory markers were present in MS patients and whether they were associated with periodontal disease (PD). Quality and bias were assessed using the Newcastle-Ottawa Scale, resulting in eight articles that were thoroughly analyzed. Results: The results point to a strong correlation between MS and periodontal disorders, which may point to the same pathophysiological mechanism. It does, however, underscore the necessity of additional study to determine a definitive causal association. Conclusions: The findings indicate a strong association between MS and PDs, likely mediated by systemic inflammatory responses detectable in saliva. The review highlights the importance of oral health in managing MS and supports the utility of saliva as a practical, non-invasive medium for monitoring systemic inflammation. Further research is necessary to confirm the causal relationships and to consider integrating salivary diagnostics into routine clinical management for MS patients.

Retrograde axonal neurodegeneration along the visual pathway-either direct or trans-synaptic-has already been demonstrated in multiple sclerosis (MS), as well as in compressive, vascular, or posttraumatic lesions of the visual pathway. Optical coherence tomography (OCT) can noninvasively track macular and optic nerve changes occurring as a result of this phenomenon. Our paper aimed to review the existing literature regarding hemimacular atrophic changes in the ganglion cell layer identified using OCT examination in MS patients without prior history of optic neuritis. Homonymous hemimacular atrophy has been described in post-chiasmal MS lesions, even in patients with normal visual field results. Temporal and nasal macular OCT evaluation should be performed separately in all MS patients, in addition to an optic nerve OCT evaluation and a visual field exam.

The treatment landscape for multiple sclerosis has dramatically grown in terms of available options and complexity. The various mechanisms of action and safety profiles of these new treatments necessitate that primary care providers remain current in knowledge and practice to provide high-quality care.

OBJECTIVE: This systematic review and meta-analysis address the evidence on the association of psychological stressors with onset of multiple sclerosis, inflammatory disease activity (relapses or new disease activity on magnetic resonance imaging, MRI) and disability progression.
METHODS: PubMed was searched from 1946 to 15 July 2022. Studies and certain stressors were selected when they assessed stressors independent from stress elicited by the disease process itself. Risk of bias was assessed by the CASP Case Control Study Checklist and the CASP Cohort Study Checklist. Normal-Normal Hierarchical Model (NNHM) for random-effects meta-analysis was used in the Bayesian framework.
RESULTS: 30 studies reporting data from 26 cohorts reporting on 24.781 cases could be identified. Ten studies addressed stressors and MS disease onset showing a weak to modest effect of psychological stressors. A meta-analysis of three studies investigating diagnosed stress disorders and MS risk showed a 1.87-fold (CI 1.061 to 3.429) increased MS risk. Stress and MS relapse risk were addressed in 19 heterogeneous studies. Meta-analyses from two independent cohorts investigating the same military threat of a population showed a threefold increased risk for relapses in association with war (relapse rate: 3.0, CI 1.56 to 5.81). In addition, two studies confirmed an association of stressful life events and MRI activity. Three studies of stressors and disease progression were included indicating some effect on disease progression.
CONCLUSIONS: Taken together studies indicate a minor to modest impact of psychological stressors on disease onset, inflammatory activity and progression of MS. Possible case-selection bias and lack of confounder analysis were present in many studies.

Diet and inflammation may contribute to the development of multiple sclerosis (MS). The aim of this systematic review and meta-analysis was to assess the association between proinflammatory diet, as estimated by the Dietary Inflammatory Index (DII®), and the likelihood of developing MS or other demyelinating autoimmune diseases. A systematic search was performed of search engines and databases (PubMed, ISI Web of Sciences, Scopus, and Embase) to identify relevant studies before 10th June 2023. The search identified 182 potential studies, from which 39 full-text articles were screened for relevance. Five articles with case-control design (n = 4,322, intervention group: 1714; control group: 2608) met the study inclusion criteria. The exposure variable was DII, with studies using two distinct models: quartile-based comparisons of DII and assessment of continuous DII. The meta-analysis of high versus low quartiles of DII with four effect sizes showed a significant association with MS/demyelinating autoimmune disease likelihood, with an odds ratio (OR) of 3.26 (95% confidence interval (CI) 1.16, 9.10). The meta-analysis of four studies with DII fit as a continuous variable showed a 31% increased likelihood of MS per unit increment; which was not statistically significant at the nominal alpha equals 0.05 (OR 1.31; 95% CI 0.95, 1.81). In conclusion, this systematic review and meta-analysis provides evidence of a positive association between higher DII scores with the likelihood of developing MS, highlighting that diet-induced inflammation could play a role in MS or other demyelinating autoimmune diseases risk.

Multiple sclerosis (MS) is characterized by a variety of symptoms that have a major impact on quality of life (QoL) even in early stages. In addition to individual motor, sensory, visual disturbances, and brainstem and sphincter disorders, which are expressed through the widely used Expanded Disability Status Scale (EDSS), other manifestations of MS have a detrimental effect on overall functioning and quality of life, such as cognitive impairment, depression, anxiety, fatigue, and pain. However, when talking about QoL, categorical definitions cannot be used because although the concept is generally understood, it is highly nuanced. Suffering from MS can significantly reduce QoL. Numerous research studies have focused on trying to identify and assess which are the elements that most affect the loss of QoL in MS people. However, in addition to the fact that the measurement of QoL can be subjective, it is very difficult to consider these elements in isolation, as they are interrelated. One such limiting factor of QoL that has been investigated is cognitive impairment (CI). This has been shown to have an impact on the lives of MS people, although the different approaches that have been taken to assess CI have evident limitations.

BACKGROUND: While many studies have examined relationships of neuroimaging variables to cognitive measures in multiple sclerosis (MS), longitudinal studies are lacking. The relationship of cognitive changes to neuroradiological changes in MS is thus incompletely understood. The present study systematically reviews all studies reporting a relationship between MRI changes and cognitive changes after at least one year of follow-up.
METHODS: An extensive and methodical search of online databases was conducted to identify qualified studies until August 2023. Among various cognitive tests and magnetic resonance imaging (MRI) measures, Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test (PASAT), verbal fluency, T2 lesion volume (T2LV), white matter lesion volume (WML), and grey matter volume (GMV) qualified for inclusion in a meta-analysis investigating the association of cognitive changes to neuroradiological changes.
RESULTS: We identified 35 studies that explored the link between MRI changes and changes in cognitive outcomes. Of these, twenty studies (57.14%) investigated the association between SDMT/PASAT and MRI metrics. Eleven studies (31.42%) focused on the relationship between MRI metrics and verbal learning and memory, while ten studies (28.57%) reported associations with visuospatial learning and memory. Furthermore, eight studies (22.85%) analyzed the correlation between verbal fluency and MRI measures. Only 5 were eligible for inclusion in the meta-analysis. The meta-analysis evaluated correlations between SDMT/PASAT and GMV (rs = 0.67, 95% CI 0.44-0.91), and verbal fluency and T2LV (rs = 0.35, 95% CI 0.09-0.60).
CONCLUSIONS: In this rigorously conducted systematic review, we found a significant association of cognitive changes, specifically SDMT/PASAT and verbal fluency, to changes in T2LV and atrophy in individuals with MS. Findings should be interpreted cautiously due to the limited amount of high-quality research, small sample sizes, and variability in study methodologies.

BACKGROUND: Several studies have shown the different relationships between cognitive functions and structural magnetic resonance imaging (MRI) measurements in people with multiple sclerosis (pwMS). However, there is an ongoing debate regarding the magnitude of correlation between MRI measurements and specific cognitive function tests. This systematic review and meta-analysis aimed to synthesize the most consistent correlations between MRI measurements and cognitive function in pwMS.
METHODS: PubMed/MEDLINE, Embase, Scopus, and Web of Science databases were systematically searched up to February 2023, to find relevant data. The search utilized syntax and medical subject headings (MeSH) relevant to cognitive performance tests and MRI measurements in pwMS. The R software version 4.3.3 with random effect models was used to estimate the pooled effect sizes.
RESULTS: 13,559 studies were reviewed, of which 136 were included. The meta-analyses showed that thalamic volume had the most significant correlations with Symbol Digit Modalities Test (SDMT) r = 0.47 (95 % CI: 0.39 to 0.56, p < 0.001, I2 = 88 %), Brief Visual Memory Test-Revised-Total Recall (BVMT-TR) r = 0.51 (95 % CI: 0.36 to 0.66, p < 0.001, I2 = 81 %), California Verbal Learning Test-II-Total Recall (CVLT-TR) r = 0.47 (95 % CI: 0.34 to 0.59, p < 0.001, I2 = 69 %,), and Delis-Kaplan Executive Function System (DKEFS) r = 0.48 (95 % CI: 0.34 to 0.63, p < 0.001, I2 = 22 %,).
CONCLUSIONS: We conclude that thalamic volume exhibits highest relationships with information processing speed (IPS), visuospatial learning-memory, verbal learning-memory, and executive function in pwMS. A comprehensive understanding of the intricacies of the mechanisms underpinning this association requires additional research.

BACKGROUND: Autologous haematopoietic stem cell transplant (HSCT) is considered an effective treatment for highly active multiple sclerosis (MS). To date, most research has focused primarily on disease outcome measures, despite the significant impact of neuropsychological symptoms on MS patients\' quality of life. The current systematic review aimed to examine whether HSCT for MS impacts neuropsychological outcome measures such as cognition, fatigue, mood, and quality of life.
METHODS: The review was registered with the International Prospective Register of Systematic Reviews (PROSPERO, ID: CRD42023474214). Systematic searches were carried out in six databases (PsycINFO, PubMed, Embase, Scopus, CINAHL and Web of Science) based on the following inclusion criteria: (i) published in peer-reviewed journals in English; (ii) longitudinal studies of adults with MS (iii) at least one neuropsychological outcome was assessed pre- and post-HSCT using standardised measures. Risk of bias was assessed using the National Heart, Lung and Blood Institute (NHLBI) quality assessment tools. A narrative synthesis was used to present results.
RESULTS: Eleven studies were included in the review. Long-term improvements in quality of life post-HSCT were identified. In terms of cognition and fatigue, the evidence was mixed, with some post-HSCT improvements identified. Decline in cognitive performance in the short-term post-HSCT was observed. No changes in mood were identified post-HSCT. Arguments for interpreting these results with caution are presented based on risk of bias. Arguments for interpreting these results with caution are presented based on risk of bias. Limitations of the evidence are discussed, such confounding variables and lack of statistical power.
CONCLUSIONS: The evidence base for the impact of HSCT for MS on neuropsychological outcomes is limited. Further research is required to progress understanding to facilitate clinician and patient understanding of HSCT treatment for MS.