Distinct clinical, imaging, and cerebrospinal fluid profiles in people with late-onset multiple sclerosis
Introduction Late-onset multiple sclerosis (LOMS), defined as onset after age 50, poses unique diagnostic challenges due to clinical and radiological differences from early-onset multiple sclerosis (EOMS), which typically manifests in adults between 20 and 40 years of age. Limited research on these differences hampers accurate diagnosis of LOMS. This study aims to bridge this gap by comparing clinical presentation, imaging, and cerebrospinal fluid (CSF) findings in LOMS and EOMS patients. Methods We retrospectively analyzed clinical, MRI, and CSF data from 148 LOMS patients treated in the neuroimmunology outpatient clinic of a Swiss tertiary referral center between 2013 and 2023. A control group of 148 EOMS patients, matched by year of diagnosis, was included for comparison. Results LOMS patients, with a median onset age of 53 years (interquartile range (IQR) 51–58 years), more commonly presented with motor or multiple symptoms and a primary progressive multiple sclerosis subtype (p < 0.001). They were also more likely than EOMS patients (median onset age 28 years, IQR 24–33 years) to report cognitive impairment and fatigue at disease onset (p < 0.001). MRI analysis showed that LOMS patients had a significantly higher T2-lesion load (p = 0.026) but fewer Gadolinium-enhancing lesions at diagnosis (p < 0.001). The percentage of patients with CSF-specific oligoclonal bands was comparable between groups, whereas CSF pleocytosis was more common in EOMS patients (p < 0.001). Importantly, we noticed a significant delay in diagnosing multiple sclerosis in older adults likely due to misdiagnosis or difficulties in timely recognition. Discussion LOMS represents a subgroup of multiple sclerosis with unique clinical and radiological characteristics compared to EOMS. The higher T2-lesion burden and fewer Gadolinium-enhancing lesions in LOMS can pose diagnostic challenges. Recognizing these differences may enhance diagnostic accuracy and guide more effective management strategies for LOMS. Keywords Multiple sclerosis Late onset CSF Oligoclonal bands 1 Introduction Late-onset multiple sclerosis (LOMS), defined as disease onset after age 50, represents a challenging subset of multiple sclerosis (MS). A 2021 literature review reported that LOMS accounts for 1.1 % to 21.3 % of all people with MS (pwMS) (Naseri et al., 2021) with a trend toward increasing incidence in recent years (Capasso et al., 2023; Prosperini and Haggiag, 2024). Differentiating early-onset MS (EOMS), typically defined as onset between ages 18 and 40 or 50, from LOMS has long been regarded an important topic. Higher proportions of primary progressive MS (PPMS) subtypes were described in cohorts of LOMS (Mouresan et al., 2024). Clinically, some analyses suggest that patients with LOMS may be more prone to motor dysfunction, cerebellar symptoms and signs, fatigue, as well as sphincter disturbances, while EOMS patients are often reported to present more frequently with visual and sensory disturbances, although findings have not been consistent across all studies (Martinelli et al., 2004; Palathinkara et al., 2023). The burden of cognitive impairment seems to be higher in patients with LOMS, especially in the presence of vascular risk factors (Butler Pagnotti et al., 2022; Oliveira et al., 2024). Moreover, patients with LOMS often reach critical disability milestones, such as an Expanded Disability Status Scale (EDSS) score of six, more rapidly than EOMS patients (Andersen et al., 2021; D'Amico et al., 2018). However, they are less likely to be treated with high-efficacy disease modifying drugs (Knowles et al., 2024). Magnetic resonance imaging (MRI) has been used to explore potential distinctions between the two groups: patients with LOMS may have a higher incidence of spinal lesions, while EOMS patients are more likely to exhibit contrast-enhancing brain lesions (Kis et al., 2008; Palathinkara et al., 2023). Diagnosing LOMS is complicated by a higher frequency of nonspecific or vascular white matter changes on brain MRI, as well as a greater likelihood of differential diagnoses that can mimic MS in this age group. These factors may lead to diagnostic delay and false diagnoses (de Seze et al., 2005; Kis et al., 2008; Martinelli et al., 2004; Polliack et al., 2001). Consequently, incorporating cerebrospinal fluid (CSF) analysis, especially the detection of CSF-specific oligoclonal bands and other markers of inflammatory processes, is of particular importance for confirming MS diagnoses in older patients. Despite previous studies investigating clinical and imaging characteristics in LOMS and EOMS, comprehensive data on differences, particularly regarding CSF profiles and other disease features, remain limited. To address this gap, we conducted a retrospective analysis comparing the clinical, radiological, and CSF characteristics of 148 LOMS patients with 148 EOMS patients from our MS cohort.
Download
steinegger_2025.pdfResearchers
