New research shows brain tissue loss follows a predictable sequence

Dr Arman Eshaghi was awarded an MS International Federation McDonald Fellowship to travel from Iran to undertake a research project at Queen Square London looking at brain volume loss in MS.

The loss of brain volume, known as atrophy, happens at a faster rate in people with MS and seems to be linked more closely to the accumulation of disability than relapses and lesions.

In a new study, Dr Eshaghi has shown that particular areas of the brain are affected by atrophy and that the areas are affected in a particular order over time.

This type of research may lead to the possibility of determining the ’stage’ of damage in the brain due to MS and a more personalised medicine approach.

MS is triggered by the immune system mistakenly attacking the brain and spinal cord. Most of the medications currently available for MS aim to reduce these attacks to prevent further damage.

However, there is also another component of MS: the loss of brain tissue over time. Brain volume loss, or brain atrophy, occurs in everyone as we age, but it happens at a faster rate in people with MS. Previous research has also shown that, in MS, this brain volume loss can be an early feature of the disease and seems to be linked to the accumulation of disability over time – more so than the number of relapses or lesions in the brain.

Due to this link with disability, there is a great deal of interest in this process of brain volume loss. It seems that certain parts of the brain are more susceptible to atrophy than others.

New research led by Dr Arman Eshaghi at the Queen Square MS research group in London has shown that atrophy occurs in a particular sequence. Dr Eshaghi is from Iran and is currently undertaking an MSIF McDonald Fellowship. These fellowships enable young researchers from emerging countries to work in a research institution outside of their own country. At the end of the fellowship, the researchers return home to use their new skills and networks to enhance research and MS care in their own countries.

Dr Eshaghi looked at brain volume loss in people with different types of MS, people with clinically isolated syndrome (a potential precursor of MS) and people without MS. 1,424 people took part in the study, which looked at areas of brain volume loss using magnetic resonance imaging (MRI). By looking at the population as a whole, Dr Eshaghi was able to determine the areas affected by brain volume loss and for the first time identify the order in which the regions were affected.

Dr Eshaghi suspected that the pattern of brain tissue loss would be different for those people who started out with relapsing MS compared to people with primary progressive MS. In fact, the sequence of brain volume loss was reasonably consistent across the different types of MS. Areas of the brain known as the posterior cingulate cortex, precuneus, thalamus and brainstem were affected in early stages of MS, irrespective of the type of MS that a person had. The common theme between all these areas is that they are parts of the brain with many nerve connections, perhaps suggesting that areas such as these, which consume a lot of energy and are connected to multiple other areas of the brain, may be more vulnerable in MS.

Other findings

Further analysis of the people with MS in the study showed that other brain regions known as insula, accumbens and caudate were also likely to suffer tissue loss early in the disease. These regions may be part of the brain pathways involved in fatigue and cognitive function – often the earliest symptoms people report of their MS.

Dr Eshaghi also looked at changes to brain volume over time in individuals. He found that the rate of brain volume loss was related to the length of time that the individual had lived with MS, regardless of the type of MS that they had. In people with relapsing-remitting MS, brain volume loss was independently related   to the level of their disability.

This research is a great advance in improving our understanding of MS. While this study represents only the first step, future research into this area may make it possible to categorise an individual’s ‘stage’ of brain volume loss. This could help identify groups of people that may benefit from particular types of therapies based on their stage of disease, or identify people for clinical trials. This in turn would lead to better and more meaningful clinical trial results and eventually could help improve treatment decisions for people with MS in the clinic.

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