The 41st Congress of the European Committee for Treatment and Research in Multiple Sclerosis – 24-26 September 2025
The following summarizes some of the highlights from Day 1 of ECTRIMS 2025.
Saturday Edition
Friday Edition
Minimal EDSS change clinically significant
Two-fold greater risk of MS with mononucleosis
Impact of menopause on MS symptoms
GFAP a potential PIRA biomarker
PIRMA proposed
Distinct phases of brain atrophy identified
Clinical tip of the day
CONGRESS HIGHLIGHTS – THURSDAY EDITION
Minimal EDSS change clinically significant
A Swedish MS registry study reported that a small increase in EDSS score is prognostic of progression even in patients with minimal disability (Forsberg et al. ECTRIMS 2025;P060). Patients with a baseline EDSS score of 1.0-3.5 with a 0-step or 0.5-step change in EDSS over a two-year period were included in the analysis. Patients with a 0.5-step EDSS change had significantly greater disability progression at five-year follow-up compared to patients with a 0-step change. The authors noted that clinical trials typically use a ≥1-step change in EDSS as a criterion for confirmed disability progression (CDP) and progression independent of relapse activity (PIRA), which erroneously assumes that small EDSS changes are not prognostic of disability progression.
Two-fold greater risk of MS with mononucleosis
Numerous studies have reported that a history of infectious mononucleosis (IM) caused by the Epstein-Barr virus (EBV) is associated with a higher MS risk (Loosen et al. Front Immunol 2022;13:937583). An analysis of the Swedish Patient Register identified 37,722 patients diagnosed with IM in a hospital setting during the period 2001-2021 and compared them to 310,190 matched controls without a history of IM hospitalization (Banefelt et al. ECTRIMS 2025;P068). Mean age at IM diagnosis was 18.9 years; 51% were female. A total of 460 patients in the IM group subsequently developed MS. The incidence of MS was 27.8/100,000 in the IM group compared to 10.6/100,000 in the non-IM group (hazard ratio 2.60). A previous study in Denmark reported a higher MS incidence in patients previously hospitalized for IM (HR 2.47).
Impact of menopause on MS symptoms
Patients in the United Kingdom MS Register were invited to complete an online questionnaire about their experience with menopause while living with MS (Collier et al. ECTRIMS 2025;P081). A total of 3129 respondents (mean age 55.6 years) participated; mean MS duration was 14.7 years. A total of 59.0% had RRMS, 25.9% had SPMS, and 9.3% had PPMS. Patients reported being premenopausal (14.48%), perimenopausal (16.87%), postmenopausal (58.8%) or unsure (9.85%). Mean age at last menstrual period was 49 years. Overall, 95.8% of perimenopausal and 74.82% of postmenopausal patients reported menopausal symptoms such as hot flushes (70.08%), night sweats (64.35%), and sleep problems (60.47%). A total of 47.71% of perimenopausal and 23.85% of postmenopausal women reported worsening MS symptoms due to menopause, such as fatigue (72.94%), cognitive problems (56.63%) and bladder problems (55.97%). Patients used various strategies to manage menopausal symptoms, such as exercise (30.4%), diet (28.07%) and mindfulness (19.28%).
GFAP a potential PIRA biomarker
A Spanish observational study (N=210) examined fluid biomarkers in RRMS patients with vs. without a history of progression independent of relapse activity (PIRA) events (Veiga et al. ECTRIMS 2025;P240). The biomarkers assessed were serum neurofilament-light chain (sNfL), a marker of axonal damage, and glial fibrillary acidic protein (GFAP), a marker of astrocytosis. All PIRA events occurred ≤3 years prior to sample collection. Median age was 45 years; median EDSS was 3.0. One-third were receiving treatment with a monoclonal antibody. EDSS scores were significantly higher in the PIRA group (median 4.5 vs. 2.0). Median sNfL levels were higher in the PIRA group (7.44 vs. 4.61 pg/mL); most values were within the normal range, which may be attributed to a treatment effect. More informative were sGFAP levels, which were significantly higher in the PIRA group (121 vs. 78 pg/mL). The authors noted that persistently elevated sGFAP levels may reflect smouldering inflammation and may be a better predictor of disability progression.
PIRMA proposed
Progression independent of relapse activity (PIRA) purports to identify ongoing neurodegeneration that is unmasked during relapse-free periods. A limitation, however, is that it excludes MRI assessment so it does not take into account subclinical neuroinflammation and the impact of new lesions on progression. An Italian multicentre study evaluated 109 MS patients over a five-year period to determine the proportion with progression independent of relapse and MRI activity (PIRMA) (Barbuti et al. ECTRIMS 2025;P186). Mean age was 41.9 years; median EDSS score was 2.0. At five years, 33% had evidence of PIRMA. Older age and reduced cortical volume were predictors of PIRMA. The authors noted that the rates of PIRMA and PIRA may differ, but PIRMA may better identify progression independent of neuroinflammation.
Distinct phases of brain atrophy identified
Synaptic dysfunction is the first phase of a multi-stage process of brain atrophy, according to a proteonomic analysis of post-mortem brain samples (Quiroga-Varela et al. ECTRIMS 2025;P168). Fifteen tissue samples from the middle frontal gyrus were categorized by atrophy severity (mild, moderate, severe) by neuropathological criteria (brain volume, demyelination, cortical microstructure). A total of 165 proteins differentiated mild vs. moderate atrophy; 106 proteins differentiated mild vs. severe atrophy; and 99 proteins differentiated moderate vs. severe atrophy. Early atrophy was characterized by synaptic protein and immune mediators related to the synapse, post-synapse and synaptic organization. Later stages of atrophy were marked by inflammatory pathways (e.g. phagocytosis, neutrophil degranulation) and mitochondrial dysfunction affecting energy metabolism (e.g. NADH, pyruvate). The authors concluded that neuroinflammation causes synaptic dysfunction and early brain atrophy. Irreversible synaptic loss occurs when compensatory mechanisms fail.
Clinical tip of the day
When performing cognitive testing in clinical practice, a separate room may not be necessary. A Danish MS centre study administered the Processing Speed Test (PST) in the waiting room and in a quiet room in the hospital and compared results (Blinkenberg et al. ECTRIMS 2025;P051). Headphones were provided to hear auditory instructions for self-administering the test on a tablet. A total of 46 patients completed the PST under both test conditions. The overall mean PST score was 56.87 in the waiting room and 54.74 in the quiet room, suggesting that the PST can be administered when patients first arrive in the waiting room.
Saturday Edition
Friday Edition