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

Author:

Knowles Sarah1ORCID,Middleton Rod1ORCID,Cooze Benjamin2,Farkas Ildiko3,Leung Yeung Yeung3,Allen Kelsey2,Winslade Molly2,Owen David R.J.3,Magliozzi Roberta34ORCID,Reynolds Richard3,Neal James W.2,Pearson Owen5,Nicholas Richard13ORCID,Pickrell W. Owen25,Howell Owain W.23ORCID,

Affiliation:

1. UK MS Register, Swansea University Medical School Swansea University Swansea UK

2. Department of Neurosciences Swansea University Medical School, Swansea University Swansea UK

3. Division of Brain Sciences Imperial College London London UK

4. Department of Neurological and Movement Sciences University of Verona Verona Italy

5. Neurology Department Morriston Hospital, Swansea Bay University Health Board Port Talbot UK

Abstract

ObjectiveOlder people with multiple sclerosis (MS) have a less active radiological and clinical presentation, but many still attain significant levels of disability; but what drives worsening disability in this group?MethodsWe used data from the UK MS Register to characterize demographics and clinical features of late‐onset multiple sclerosis (LOMS; symptom onset at ≥50 years), compared with 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, mean age of onset 29 years).ResultsIn the Register cohort, there were 1,608 (9.4%) with LOMS. When compared with AOMS, there was a lower proportion of women, a higher proportion of primary progressive MS, a higher level of disability at diagnosis (median MS impact scale 36.7 vs. 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, whereas actively demyelinating lesions and compartmentalized inflammation was greatest in AOMS. Only neuron density, and not demyelination or the extent of compartmentalized inflammation, correlated with disability outcomes in older‐onset MS patients.InterpretationThe 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. ANN NEUROL 2023

Funder

Health and Care Research Wales

Multiple Sclerosis Society

Swansea University

Publisher

Wiley

Subject

Neurology (clinical),Neurology

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