Myelin injury precedes axonal injury and symptomatic onset in multiple sclerosis, 2025, Ahmed Abdelhak et al

Mij

Senior Member (Voting Rights)
Abstract

The timing of the biological onset of multiple sclerosis (MS) is unclear. We used high-throughput discovery proteomics and samples from pre symptomatic patients with MS and matched healthy controls to define the biological neurological onset and characterize the mechanisms involved. Remarkably, evidence of myelin injury was seen ~7 years before the symptomatic onset and preceded evidence of axonal injury by ~1 year.

By contrast, astrocyte involvement became evident only at clinical onset. Numerous changes in the serum proteome indicate the involvement of interleukin 3 and nuclear factor kappa B pathways during the pre symptomatic stage. Furthermore, people with MS with a previously reported distinct autoantibody signature showed increased immune cell activity compared to those without. We propose a protein biomarker panel that may help distinguish pre symptomatic patients with MS from healthy controls, pending validation in future studies.

Our findings can help understand the pathophysiology of MS as well as the cascade of central nervous system injury and might facilitate early detection of MS in high-risk people.
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They are asymptomatic.

"‘Presymptomatic multiple sclerosis (MS)’ is time-wise a hybrid observation.

On the one hand, the terminology refers to the increased healthcare use seen retrospectively in people with MS (pwMS) in the years before diagnosis. After excluding accounts of missed MS, this MS prodrome mainly consists of vague symptoms lacking specificity for use in clinical practice.

On the other hand, presymptomatic MS is prospectively suspected in people undergoing brain scans for unrelated conditions (e.g. headache, trauma) or screening purposes (e.g. flight attendants) who have radiological features of MS. In practice, it is only the latter that puts physicians for a treatment dilemma"
 
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