Distinct clinical, imaging, and cerebrospinal fluid profiles in people with late-onset multiple sclerosis

Lukas Steinegger; Veronika Kana; Nathalie Nierobisch; Adham Elshahabi; Michael Weller; Marina Herwerth; Patrick Roth

doi:10.1016/j.msard.2025.106399

Distinct clinical, imaging, and cerebrospinal fluid profiles in people with late-onset multiple sclerosis

Mult Scler Relat Disord. 2025 May:97:106399. doi: 10.1016/j.msard.2025.106399. Epub 2025 Mar 18.

Authors

Lukas Steinegger¹, Veronika Kana², Nathalie Nierobisch³, Adham Elshahabi², Michael Weller⁴, Marina Herwerth⁴, Patrick Roth⁴

Affiliations

¹ Department of Neurology, University Hospital Zurich and University of Zurich, Frauenklinikstrasse 26, Zurich 8091, Switzerland. Electronic address: lukas.steinegger@usz.ch.
² Department of Neurology, University Hospital Zurich and University of Zurich, Frauenklinikstrasse 26, Zurich 8091, Switzerland.
³ Neuroscience Center Zurich, University and ETH Zurich, Zurich, Switzerland; Department of Neuroradiology, University Hospital Zurich, Zurich, Switzerland.
⁴ Department of Neurology, University Hospital Zurich and University of Zurich, Frauenklinikstrasse 26, Zurich 8091, Switzerland; Neuroscience Center Zurich, University and ETH Zurich, Zurich, Switzerland.

PMID: 40147290
DOI: 10.1016/j.msard.2025.106399

Abstract

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: CSF; Late onset; Multiple sclerosis; Oligoclonal bands.

MeSH terms

Adult
Age of Onset
Female
Humans
Magnetic Resonance Imaging
Male
Middle Aged
Multiple Sclerosis* / cerebrospinal fluid
Multiple Sclerosis* / diagnosis
Multiple Sclerosis* / diagnostic imaging
Multiple Sclerosis* / pathology
Multiple Sclerosis* / physiopathology
Retrospective Studies