The damage to myelin seen in MS is caused by inflammation resulting from an immune system attack on the brain.
The level of inflammation early in the disease, captured through measuring lesions can, to an extent, predict longer-term clinical outcomes. However, this is not the full story as lesions don’t completely account for MS progression, and the second stage of MS where nerve cells are lost and disability starts to accumulate without any inflammation. This means there is an urgent need for biomarkers – things that can be measured to indicate a biological process – that can be detected earlier in the disease and more accurately predict MS progression.
A team of Australian researchers led by Ms Sanuji Gajamange, a postgraduate scholar funded by MS Research Australia, and Dr Scott Kolbe, were interested to see whether changes linked to the loss of nerve cells, measured using magnetic resonance imaging (MRI) and optical coherence tomography (measures the retinal thickness in the eye), would be able to predict longer-term MS severity.
What did the researchers do?
The researchers followed 36 people with Clinically Isolated Syndrome (CIS). CIS refers to a first attack of neurological symptoms and it can be a precursor for MS for some people. A second attack is required in order to be diagnosed with MS. The researchers looked at differences in lesion measurements and the loss of nerve cells between those who eventually developed MS and those who didn’t.
Specifically, the researchers were interested in the loss of brain tissue volume, changes in the brain structure, and the thickness of the layer of nerve cells at the back of the eye. The team looked at whether these measurements early in the disease could be used as predictors of longer-term MS severity in people at the very earliest stages of disease (those with CIS).
For those people who did go on to have a diagnosis of MS, the researchers also looked at which of these measurements over the first 12 months could predict the time to a second relapse (and therefore a diagnosis of MS), the number of relapses overall and disability accumulation over many years, up to 10 years in some participants.
Lesions were different in people who went on to have MS
The researchers found that 69% of people with CIS went on to have MS. They found that there were a number of differences between the characteristics of lesions in the first 12 months in those who went to have MS and those who didn’t.
Interestingly, disease-modifying treatment had no impact on the time to second relapse. These findings suggest that inflammatory activity is the main driver of relapses.
What about the measurements related to nerve cell loss?
The researchers found that people who converted to MS had greater brain volume loss and more thinning of the layer of nerve cells at the back of the eye compared to people who did not go on to have MS. They also found that if this nerve layer thinning started earlier, it predicted the final level of disability seen in those people.
What do these results mean?
These exciting findings suggest that early measurements relating to the loss of nerve cells could improve the prediction of longer-term severity of MS, including disability progression. While further studies will be required, knowing whether someone is more likely to convert to MS or have worse outcomes could inform treatment decisions earlier in the disease and hopefully, prevent them.