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Comparing the Pathology, Clinical, and Demographic Characteristics of Younger and Older‐Onset Multiple Sclerosis

Sarah Knowles, Rod Middleton Orcid Logo, Benjamin Cooze, Ildiko Farkas, Yeung Yeung Leung, Kelsey Allen, MOLLY WINSLADE, David R.J. Owen, Roberta Magliozzi Orcid Logo, Richard Reynolds, James W. Neal, Owen Pearson, Richard Nicholas Orcid Logo, Owen Pickrell Orcid Logo, Owain Howell Orcid Logo, (the UK MS Register Research Group)

Annals of Neurology, Volume: 95, Issue: 3, Pages: 471 - 486

Swansea University Authors: Sarah Knowles, Rod Middleton Orcid Logo, Benjamin Cooze, Kelsey Allen, MOLLY WINSLADE, Owen Pickrell Orcid Logo, Owain Howell Orcid Logo

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DOI (Published version): 10.1002/ana.26843

Abstract

Objective: Older people with multiple sclerosis have a less active radiological and clinical presentation, but many still attain significant levels of disability; but what drives worsening disability in this group?Methods: We used data from the UK MS Register to characterise demographics and clinica...

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Published in: Annals of Neurology
ISSN: 0364-5134 1531-8249
Published: Wiley 2024
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URI: https://cronfa.swan.ac.uk/Record/cronfa65353
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Abstract: Objective: Older people with multiple sclerosis have a less active radiological and clinical presentation, but many still attain significant levels of disability; but what drives worsening disability in this group?Methods: We used data from the UK MS Register to characterise demographics and clinical features of late-onset multiple sclerosis (LOMS; symptom onset at ≥50 years), compared to adult-onset MS (AOMS; onset 18-49 years). We performed a pathology study of a separate MS cohort with a later onset (n=18, mean age of onset 54 years) versus AOMS (n=23, age of onset 30 years).Results: In the Register cohort there were 1608 (9.4%) with LOMS. When compared with AOMS, there was a lower proportion of females, a higher proportion of primary progressive MS, a higher level of disability at diagnosis (median MS impact scale 36.7 v 28.3, p<0.001), and a higher proportion of gait-related initial symptoms. People with LOMS were less likely to receive a high efficacy disease modifying treatment and attained substantial disability sooner.Controlling for age of death and sex, neuron density in the thalamus and pons decreased with onset-age, whilst actively demyelinating lesions and compartmentalised inflammation was greatest in AOMS. Only neuron density, and not demyelination or the extent of compartmentalised inflammation, correlated with disability outcomes in older-onset MS.Interpretation: The more progressive nature of older-onset MS is associated with significant neurodegeneration but infrequent inflammatory demyelination. These findings have implications for the assessment and treatment of MS in older people.
Keywords: Multiple Sclerosis, Disability
College: Swansea University Medical School
Funders: Multiple Sclerosis Society HCRW BRAIN unit
Issue: 3
Start Page: 471
End Page: 486