Research published in Brain1 has used new MRI techniques to show what is happening in the brains of people with multiple sclerosis (MS) in the early stages of their condition. Scientists say these previously unseen changes could have the potential to predict how disabled a person might become in the future.
MS can cause a range of symptoms, including fatigue, vision problems, numbness, pain and mobility problems. It’s unpredictable and different for everyone, and the uncertainty of how the condition will develop – both in terms of symptoms and severity – is often a major cause of concern for those affected. This uncertainty depends also on the fact that MRI, the primary tool used to diagnose and follow up MS patients, can only see a small part of the complex MS damage that occurs.
Funded by the MS Society and Rosetrees Trust, this University College London (UCL) study combined advanced MRI techniques to show microscopic changes happening in the MS brain. The team at the Queen Square MS Centre observed 42 people who had experienced their first MS symptoms in the previous three months and, compared to healthy volunteers, found their MRIs showed alterations in sodium concentration, a fundamental element for our brain function, and the brain microstructure.
Crucially, the scale of these changes corresponded to subtle signs of disability, like slower walking speed and higher EDSS score*, suggesting these previously undetectable changes could be contributing to such disability. If they also prove to be related to disability build-up, they could even be used to more accurately predict how someone’s MS will affect them in the future – though further longitudinal research on the 42 subjects is still going on.
Dr Sara Collorone, a neurologist and Clinical Research Associate at UCL and author of the study, said: “MRI plays a vital role in how we diagnose MS and monitor it throughout someone’s life, and that has been the case for decades. But traditional techniques don’t tell us the whole story.
“This development is exciting because these new techniques go way beyond what we can do with conventional MRI, allowing us to see damage and alterations in brain tissue that we haven’t seen before in early MS. This approach can provide valuable information about early MS damage that previously has only been obtainable through post-mortem studies on brain tissue from people with advanced MS. By providing clues on how MS will progress, it is hoped these techniques will lead to a better long-term prognosis for the newly diagnosed – as well as greater certainty for the future.”
The conventional MRI findings used in practice today are unable to show the clinical variability of MS. Currently, white matter lesions in the brain and spinal cord are visible as white spots on an MRI scan, but these white spots provide comparatively little information on the degree or scale of damage, and the study found no association between white matter lesions and disability.
Disability in MS is driven both by inflammation and nerve loss, with the latter causing the gradually worsening, irreversible disability seen in progressive forms of MS. The alterations visible using these new techniques are indicative of damage to nerves, and may prove to be a very early indication of the likelihood of progressive disease. If this is confirmed in further long-term studies, clinicians could translate that knowledge into more targeted use of treatments in early MS, improving patients’ prognosis. Such understanding could be particularly important if neuroprotective drugs start to emerge – a goal the MS Society’s Stop MS Appeal is striving towards within the next five years.
Dr Emma Gray, Assistant Director of Research at the MS Society, said: “MS is incredibly unpredictable, and giving people greater certainty about their future is one of our top organisational goals. We’re really proud to have funded this research, which could help provide that certainty.
“The next step is for the team to continue the follow-up study of this group of people living with MS, and confirm whether there is a link between these changes and how someone’s MS develops. If the changes can predict later disability this will be a game-changer for how the condition is managed, how future clinical trials are run, and eventually give people with MS the information they need to plan for their future.”
Amy Thompson, 24, lives in Manchester and has the relapsing remitting form of MS. She said: “Most people living with MS, including myself, would say the worst part about their illness is its unpredictability and not knowing what the future might look like. No one really knows what tomorrow will bring, and from that side of things this technology is very positive. I think it’s really important people have the option of knowing how their MS could progress, so their treatment can be tailored to them – at the moment it’s all a bit of a guessing game.
“I know some people might not want to know how bad their MS could get, but knowing would help in lots of other ways. It would help me to plan ahead, and generally reduce some of my anxiety about what the future might hold. And even if I was told it wasn’t looking good, that would motivate me to do everything while I still can. Some people could go the other way and be affected negatively, but I personally feel like knowing what’s round the corner would put you in a better position. So you could get the best possible treatment and care, and live well with your MS.”
Leading Welsh Neuro-Rehabilitation Expert, Sara Davis from NeuroPhysio Wales, welcomed the research. Sara said:
“Working with MS patients in our clinic regularly gives us a real insight into how the disease progresses in individuals, and it definitely isn’t ‘one disease fits all’ – every patient is different and it’s therefore not surprising that every prognosis is too.
“This new MRI technique brings a better outcome for patients that much closer. Having a clearer understanding of prognosis from the word go will enable neurophysiotherapists to effectively tailor their exercise and rehabilitation programmes for MS patients with long term goals in mind – we continue to be amazed at the power of the nervous system – and the more we learn how the disease progresses in individuals, the closer we are to finding an effective treatment for everyone.”
The MS Society’s Stop MS Appeal needs to raise £100million to find treatments for everyone with MS. With your help, we can reach our target and stop MS. For more information visit www.mssociety.org.uk/STOP-MS.
*The Expanded Disability Status Scale (EDSS) is a method of quantifying disability in multiple sclerosis and monitoring changes in the level of disability over time.
1. Collorone et al. Brain microstructural and metabolic alterations at the onset of the first demyelinating event. Available online from 00.01 GMT Tuesday 27 April 2021
About the study
In this cross-sectional study, they enrolled 42 patients diagnosed with clinically isolated syndrome or multiple sclerosis within three months of their first demyelinating event and 16 healthy controls. They combined, for the first time, two new techniques named NODDI (Neurite Orientation Dispersion and Density Imaging) and 23Na MRI (Sodium Magnetic Resonance Imaging). Through these, researchers have been able to obtain information on underlying, microscopic changes in the brain, including changes to the structure of neurons and sodium concentration, which are not detected by conventional MRI.
The next step for the team will be to conduct a larger follow up study, to establish if the changes that have been visible through these MRIs are related to disability accrual over the next five years.
About multiple sclerosis and the MS Society
· Over 130,000 people live with multiple sclerosis (MS) in the UK
· MS damages nerves in your body and makes it harder to do everyday things, like walk, talk, eat and think
· It’s relentless, painful, and disabling
· It can be unpredictable and different for everyone
· The MS Society is here to make life better for people with MS, through research, campaigning, and support.
· We have a free helpline – 0808 800 8000 and information can be found on our website www.mssociety.org.uk
· We’re driving research into more – and better – treatments for everyone
· Together we’re strong enough to stop MS