Mapping the order in which brain regions shrink in multiple sclerosis

Grey matter atrophy is present from the earliest stages of multiple sclerosis. What was not known was its ordering — whether regions become atrophic in a reproducible sequence, as they do in other neurodegenerative diseases, or more or less at random.

This longitudinal Brain study, first-authored by Dr Arman Eshaghi, pooled 3,604 MRI scans from 1,417 people across seven European centres: 253 with clinically isolated syndrome, 708 relapsing-remitting, 128 secondary progressive, 125 primary progressive, and 203 healthy controls, followed for a mean of 2.41 years. Regional grey matter and brainstem volumes were computed against an unbiased within-subject template, and an established event-based model was used to infer the sequence of atrophy events and the uncertainty around it. Each participant could then be assigned a stage based on how many of their regions had become atrophic.

Placing people on a common staging axis — rather than comparing group averages — makes it possible to ask how fast an individual is moving through the sequence, and to relate that rate to lesion load, disease-modifying treatment and disability accumulation. The paper drew a scientific commentary in the same issue, and the staging approach it introduced underpins much of the later MS-PINPOINT work on data-driven disease models.

Read the paper: Progression of regional grey matter atrophy in multiple sclerosis.