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.