Brain volume changes may be key indicator for MS progression

• Brain atrophy or brain shrinkage is a normal process of aging, which may be accelerated in people with MS
• The rate of brain atrophy may be an important indicator of disease progression in MS
• Brain atrophy may be an important MRI readout offering additional information over and above brain lesions

Brain atrophy, or brain shrinkage, is a normal process of ageing that happens to us all once we reach our mid-20s. There are many theories on why this occurs and there can be different factors that may affect the rate at which our brains lose volume.

On average, we lose between 0.5% – 1% of our brain volume per year. Although this varies from person to person, for people with MS, this percentage can be slightly higher. Measuring the rate of brain atrophy requires regular high quality MRI scans and complex calculations to work out the volume of the brain and the amount that it changes over time – a challenging process.

Though challenging, this process can provide valuable information about brain atrophy over and above other the readings from MRI scans, such as the location and size of brain lesions. While lesions are routinely used as a marker, their number, size and location do not always correlate with the disability someone might have or develop.

It is very important that we have good markers to predict disease course and accurately monitor disease to help prevent the accumulation of disabilities and halt the progression of disease activity. A group of international scientists from the UK, Europe and the US have been investigating brain atrophy in people with primary progressive MS. In this study, published in Annals of Clinical and Translational Neurology, they used the control (untreated) group participating in a clinical trial of fingolimod in progressive MS, known as the INFORMS trial. By using this group, the researchers were able to take advantage of all the in-depth data previously collected on these 487 people with primary progressive MS, including multiple MRI images of their brains and clinical observations.

During the study, these participants showed low levels of inflammation in the brain as determined by new or growing lesions seen by their MRIs, despite the continued progression of their disability. They also had a low level of relapses, although their MRIs did reveal evidence of previous substantial inflammatory activity.

However, when the scientists looked at the rate of brain loss, they discovered that there was a relationship between the amount of brain volume lost and disability progression. Those who experienced the greatest loss of brain volume ended up with more marked disability and disease progression at the end of the study period. These results suggest there is a relationship between brain volume loss and disease progression in people with primary progressive MS, which is consistent with data from those with relapsing remitting MS.

In this study, the lack of active inflammation as shown by MRI lesions in people with primary progressive MS suggests that brain volume loss is not dependent on levels of inflammation in the brain. This potentially explains why some anti-inflammatory treatments that have been successful in relapsing remitting MS have not been so successful in primary progressive MS.

One of the challenges facing the development of medications for primary progressive MS is the lack of markers which can be used in clinical trials to determine whether or not any intervention is working. Results from this study reinforce the notion that new lesions or growing lesions as seen by MRI are not suitable markers for primary progressive MS.

Instead, brain volume measurements might be at least in part a suitable marker to help us speed up the discovery of new drugs to treat progressive MS. Other related, ongoing research indicates that brain volume loss in specific parts of the brain may be even more sensitive markers for disease progression than whole brain volume.

With thanks to MS Research Australia – the lead provider of research summaries on our website.