In MS, there are periods when the immune system suddenly attacks parts of the brain and spinal cord, causing significant damage in specific areas, called lesions. This damage can result in MS relapses.
In recent years, it has become clear that there is a second process going on in many people with MS, where some MS lesions continue growing more slowly.
On brain imaging (magnetic resonance imaging), this process is detected as slow growth of lesions over time, called “chronic lesion expansion”.
The ongoing slow immune attack around the edge of these older lesions is often called “slow burning” or “smouldering” inflammation.
The aim of Mr Kilstorner’s PhD project was to learn more about smouldering inflammation in people with progressive MS.
This requires precise measurement and sensitive analysis of lesion changes over time on imaging.
This project explored how some MS lesions continue to slowly grow over many years.
Slow-burning inflammation was a very individual feature. Some people had lesions that barely changed, while others experienced steady, ongoing growth. The speed of lesion growth was exceptionally stable for each person over time. This rate was so stable that it acted almost like a personal “disease signature”.
Importantly, this slow lesion growth happened independently of MS relapses. However, it was closely linked to shrinkage of the brain, especially in the central parts of the brain, and was also linked to increased physical disability over time.
This may help explain why some people’s disability worsens despite having no obvious relapses.
The team also found that lesion growth is not the same across the brain but follows a distinct pattern. Lesions that were closer to the fluid-filled spaces in the centre of the brain, called the ventricles, grew faster and caused more damage to the brain tissue.
Even in the parts of the brain that look normal on regular imaging, there were similar abnormalities closer to the ventricles, detected using more sensitive measures.
This gives a clue that the damage might be caused by factors found in the cerebrospinal fluid that fills the ventricles.
Building on this, the team looked at an important structure inside the ventricles, called the choroid plexus. This is a small network of tiny blood vessels and other cells that makes cerebrospinal fluid. The size of the choroid plexus, and its growth over time, was linked to lesion growth and brain shrinkage. This suggests the choroid plexus might be important in driving or maintaining smouldering inflammation.
These findings suggest that smouldering inflammation at the edge of chronic lesions is a key driver of long-term damage in MS.
Because lesion growth stays stable within individuals, it could be helpful in tracking disease progression or response to treatment.
Overall, this work helps us better understand silent MS progression and provides a way to track it using advanced brain imaging.
As part of this project, the team developed an artificial intelligence (AI)-based model to assist in modelling chronic expansion of the lesions in a fast and partly automated way. This project has attracted international collaborations with UK, Spain, Finland, and Germany.
Klistorner, S., Barnett, M., Parratt, J., Yiannikas, C., & Klistorner, A. (2025). Evolution of chronic lesion tissue in RRMS patients: An association with disease progression. Neurol Neuroimmunol Neuroinflamm 12(3):e200377. doi: 10.1212/NXI.0000000000200377
Klistorner, S., Barnett, M. H., Wang, C., Parratt, J., Yiannikas, C., & Klistorner, A. (2024). Longitudinal enlargement of choroid plexus is associated with chronic lesion expansion and neurodegeneration in RRMS patients. Multiple Sclerosis Journal, 30(4–5), 496–504.
Klistorner, S., Barnett, M. H., Parratt, J., Yiannikas, C., & Klistorner, A. (2023). Short-term surrogate biomarkers of chronic lesion expansion. medRxiv, 2023-04.
Klistorner, S., Van der Walt, A., Barnett, M. H., Butzkueven, H., Kolbe, S., Parratt, J., Yiannikas, C., & Klistorner, A.(2023). Choroid plexus volume is enlarged in clinically isolated syndrome patients with optic neuritis. Multiple Sclerosis Journal, 29(4–5), 540-548. https://doi.org/10.1177/13524585231157206
Klistorner, S., Barnett, M. H., Parratt, J., Yiannikas, C., Graham, S. L., & Klistorner, A. (2022). Choroid plexus volume in multiple sclerosis predicts expansion of chronic lesions and brain atrophy. Annals of Clinical and Translational Neurology, 9(10), 1528–1537. https://doi.org/10.1002/acn3.51644
Klistorner, S., Barnett, M. H., Graham, S. L., Wang, C., & Klistorner, A. (2022). The expansion and severity of chronic MS lesions follows a periventricular gradient. Multiple Sclerosis Journal, 28(10), 1504–1514. https://doi.org/10.1177/13524585221080667
Klistorner, S., Barnett, M. H., & Klistorner, A. (2022). Mechanisms of central brain atrophy in multiple sclerosis. Multiple Sclerosis Journal, 28(13), 2038–2045. https://doi.org/10.1177/13524585221111684
Updated 31 March 2025
$105,000
2022
3 years
Current project
