FutureMS scientific publications
FutureMS scientific publications
What findings and new insights have come from the FutureMS study so far?
Below are short descriptions of each publication.You can also view the summary on Google Scholar.
2024
Suicidal ideation in the year following diagnosis of relapsing-remitting multiple sclerosis: A longitudinal perspective
Psychological distress is common in people living with multiple sclerosis. Most previous research has looked at depression and anxiety, but it appears that suicidal thoughts (thoughts of not wanting to live) are experienced by some people too. Although there have been studies have investigated suicidal thoughts in people who have lived with MS for many years; the researchers did not find any studies that had looked at whether people experience thoughts of this kind soon after diagnosis.
The researchers looked at how common it was for people in the FutureMS study to report suicidal thoughts (ranging from mild to severe) within weeks of their MS diagnosis and 12 months after diagnosis. They found that 1 in 8 people reported suicidal thinking at the first time point (right after diagnosis) and the figure was 1 in 10 at the 12-month point. For most people (about two thirds), these thoughts were at the milder end of the severity scale. People who reported suicidal thoughts were more likely to be depressed, anxious, fatigued and to have spasms and difficulties with bladder control.
It is important that doctors and other clinicians pick up suicidal thoughts when they are present, and to know which patients are most likely to experience them. They can be very distressing and can put people at risk of self-harm. The researchers suggest patients should be asked about their mood at the time of diagnosis, using questionnaires that can pick up suicidal thoughts.
Gillespie DC, Sacripante R, Chandran S, Foley P; FutureMS consortium. Suicidal ideation in the year following diagnosis of relapsing-remitting multiple sclerosis: A longitudinal perspective. Mult Scler Relat Disord. 2024 Sep 23;91:105904. doi: 10.1016/j.msard.2024.105904.
Fatigue in early multiple sclerosis: MRI metrics of neuroinflammation, relapse and neurodegeneration
Many people living with MS experience fatigue. Unfortunately, it is not fully understood why this is the case. MRI scans of the brain and spinal cord can show inflammation and damage in the nervous system of people living with MS, which may explain why people with MS experience fatigue. Previous studies, however, have not been able to consistently show a clear connection between MRI findings and fatigue. We need a better understanding of how MS causes fatigue, which could lead to better treatments.
The researchers used data from the FutureMS cohort to look at the relationship between fatigue and inflammation or damage on standard MRI scans. They were unable to find a relationship, which, as this finding is based on a large study, helps resolve uncertainty from previous studies. The researchers also found that fatigue was common even in people with early MS who don't show signs of active MS.
Importantly, this means that fatigue should always be discussed in MS care, regardless of MS relapses.
Overall, fatigue is an important symptom in people with MS and cannot be explained by standard MRI scans. Further research is needed to better understand fatigue in people with MS. The next steps are to use more advanced MRI scans to try and identify underlying causes of fatigue.
Meijboom R, Foley P, MacDougall NJJ, Mina Y, York EN, Kampaite A, Mollison D, Kearns PKA, White N, Thrippleton MJ, Murray K, Valdés Hernández MDC, Reich DS, Connick P, Jacobson S, Nair G, Chandran S, Waldman AD. Fatigue in early multiple sclerosis: MRI metrics of neuroinflammation, relapse and neurodegeneration. Brain Commun. 2024 Aug 14;6(5):fcae278. doi: 10.1093/braincomms/fcae278.
Brain connectivity changes underlying depression and fatigue in relapsing-remitting multiple sclerosis: A systematic review.
Brain connectivity refers to how different parts of the brain communicate and work together, and in MS this communication is disrupted. Brain nerve cell axons and myelin enable connectivity. Axons are like wires that carry electrical signals between nerve cells, allowing messages to be sent back and forth. Myelin, the protective coating around axons, acts like insulation around these wires. Disruption of these connections impacts brain functioning and can potentially cause symptoms like fatigue and depression. Sophisticated MRI brain scanning techniques can study changes in brain connectivity. The researchers reviewed findings from 60 previous studies investigating the relationship between brain connectivity, and tiredness/low mood in people with MS. About half of these studies did not find a link between brain connectivity and these symptoms. The remaining studies, however, linked fatigue and depression to specific altered brain connectivity, suggesting that MS-related changes in brain connectivity may contribute to low mood and tiredness. Overall, this literature review highlights the need for more research using sophisticated MRI techniques to better understand the relationships between brain connectivity and fatigue and depression. Understanding this link could lead to better treatments and improved quality of life for people with MS.
Kampaite A, Gustafsson R, York EN, Foley P, MacDougall NJJ, Bastin ME, Chandran S, Waldman AD, Meijboom R. PLoS One. 2024 Mar 29;19(3):e0299634.doi: 0.1371/journal.pone.0299634
2023
Quantitative T1 brain mapping in early relapsing-remitting multiple sclerosis: longitudinal changes, lesion heterogeneity and disability
MS varies a great deal between individuals. It is difficult to predict if and when somebody’s MS will get worse. Advanced magnetic resonance imaging (MRI) brain scans may be able to help predict disability progression to improve treatment decision-making and future planning. Here, researchers used brain scan data from people in the FutureMS study, and healthy individuals, to test an advanced MRI technique called quantitative T1 brain mapping. Using brain scans taken shortly after MS diagnosis and again one year later, they found that T1 mapping detected early damage in the brain associated with worsening disability. They also found that areas of increased damage within brain lesions can be objectively measured with T1 mapping, and are linked to worsening disability. Quantitative T1 mapping offers a promising tool for tracking brain damage in MS.
Harper JG, York EN, Meijboom R, Kampaite A, Thrippleton MJ, Kearns PKA, Valdés Hernández MDC, Chandran S, Waldman AD; FutureMS consortium. Eur Radiol. 2024 Jun;34(6):3826-3839. doi: 10.1007/s00330-023-10351-6
Patterns of brain atrophy in recently-diagnosed relapsing-remitting multiple sclerosis
It has been thought that in MS, repeated episodes of inflammation in the brain can, over time, lead to the death and degeneration of brain cells (neurons), resulting in brain atrophy. Brain atrophy can be measured on a brain scan as shrinkage. Sophisticated analyses of MRI scans can be used to measure brain atrophy in great detail across many different regions of the brain. Here, the brain scans of 354 people in the FutureMS cohort were compared between two scans: the first taken shortly after diagnosis and the second 1 year later. The study confirmed that there was indeed brain atrophy in the 1 year scans, which was concentrated in particular brain regions. The power of using such large number of scans is that it takes account of individual variation and ‘outliers’, and is therefore more likely to give a ‘real’ result. These findings are very important for understanding the patterns of neurodegeneration in MS; they will help doctors better monitor disease progression, and help better measure the effects of drugs in clinical trials.
Meijboom R, York EN, Kampaite A, Harris MA, White N, Valdés Hernández MDC, Thrippleton MJ, MacDougall NJJ, Connick P, Hunt DPJ, Chandran S, Waldman AD; FutureMS Consortium. PLoS One. 2023 Jul 28;18(7):e0288967. doi: 10.1371/journal.pone.0288967
Pain and cognitive performance in adults with multiple sclerosis: A systematic review
In this study, the researchers reviewed all the previous published studies that have investigated the relationship between pain in people with MS and their scores on tests of thinking, learning and memory (cognitive tests). The researchers wanted to find out if there is enough evidence to draw definitive conclusions about whether pain in MS affects cognitive ability. Most of the studies reviewed did reveal that people with MS who experience higher levels of pain perform worse on cognitive tests. However, the researchers found that most of the studies were at risk of bias, and differences in methodology between studies made it impossible to compare the studies in a scientific way. Overall, the reviewers found that there likely is a connection between pain and cognitive performance in MS, but that further research is needed to better understand how they are connected.
Brown FS, Glasmacher SA, Taylor D, Jenkins R, Chandran S, Gillespie D, Foley P. Multiple Sclerosis and Related Disorders. 2023 Feb 19;71:104584. doi: 10.1016/j.msard.2023.104584
Network analysis characterizes key associations between subjective fatigue and specific depressive symptoms in early relapsing-remitting multiple sclerosis
Fatigue is a common complaint among people with MS, but its wider effects are not well understood. It’s important to understand how fatigue affects people with MS, so that they can be treated better. In this publication, the researchers studied the answers that people in the FutureMS cohort had given in questionnaires about their health and experiences of MS. The found that fatigue was particularly correlated with specific symptoms of depression, suggesting that they share pathways in the brain. Interestingly, fatigue was not associated with cognitive performance (tests of thinking, learning and memory) or brain imaging findings. These findings could guide the development of focused therapies for people with relapsing-remitting MS.
Chang YT, Kearns PKA, Carson A, Gillespie DC, Meijboom R, Kampaite A, Valdés Hernández MC, Weaver C, Stenson A, MacDougall N, O'Riordan J, Macleod MA, Carod-Artal FJ, Connick P, Waldman AD, Chandran S, Foley P. Multiple Sclerosis and Related Disorders. 2023 Jan 1;69:104429. doi: 10.1016/j.msard.2022.104429
2022
Longitudinal retinal imaging study of newly diagnosed relapsing-remitting multiple sclerosis in Scottish population: baseline and 12 months follow-up profile of FutureMS retinal imaging cohort
The eye is sometimes referred to as a “window to the brain”. Imaging the retina, the layer at the back of the eye is easy, painless and cheap, and can lead to insights into brain health. This was a proof-of-concept study to examine whether it can be useful to image the retina in MS. A subset of the FutureMS cohort agreed to take part in the study and have retinal images taken shortly after diagnosis and again 1 year later. The results showed that retinal abnormalities can be detected in people with MS soon after diagnosis, that these changes may reflect brain changes, and might help predict disease activity. This study has paved the way for further work that could aid in MS diagnosis and guide future treatments.
Chen Y, Larraz J, Wong M, et al. BMJ Open Ophthalmology 2022;7:e001024. doi: 10.1136/bmjophth-2022-001024
The influence of disease-modifying therapy on hidden disability burden in people with newly diagnosed relapsing-remitting multiple sclerosis
"Hidden disability" such as depression, anxiety, fatigue, sleep disturbance, cognitive (thinking, learning and memory) impairment and pain is a major complaint of people with MS, yet it is poorly recognised and treated. This study used the FutureMS cohort to examine what proportion of people newly diagnosed with MS experience hidden disability, and whether treatment drugs help with these symptoms. The study found that most people newly diagnosed with MS experience hidden disability, and that in most cases, this did not change over 1 year. Importantly overall findings suggested that the MS drugs that people started taking did not improve the symptoms of hidden disability, although there were hints of positive effects for a couple of them. This study has highlighted the importance of hidden disability in MS, and the unmet need early intervention in managing these elements of the condition.
Glasmacher SA, Kearns PKA, Hassan Z, Connick P, Tauber S, Reetz K, Foley P, Chandran S. Multiple Sclerosis and Related Disorders. 2022 Jul 1;63:103837. doi: 10.1016/j.msard.2022.103837
Logistic Regression–Based Model Is More Efficient Than U-Net Model for Reliable Whole Brain Magnetic Resonance Imaging Segmentation
This technical study was a comparison of two different methods for computer-based analysis of brain scan images. Scientists in this field are working on machine-learning / artificial intelligence (AI) methods to improve the interpretation of brain scans by doctors, as computers can be particularly good at spotting and measuring abnormalities on the scan faster and more accurately than a human can. Being able to extract more detailed information from brain scans can help monitor disease progression and measure the effects of therapeutic drugs.
Dieckhaus H, Meijboom R, Okar S, Wu T, Parvathaneni P, Mina Y, Chandran S, Waldman AD, Reich D, Nair G. Topics in Magnetic Resonance Imaging 31(3):p 31-39, June 2022. doi:10.1097/RMR.0000000000000296
FutureMS cohort profile: a Scottish multicentre inception cohort study of relapsing-remitting multiple sclerosis
This is an ‘introductory’ publication that describes what the FutureMS study is, and describes the characteristics of the 440 people who are part of the study cohort. Of course, no names are given and no individual is identifiable. The publication describes the geographical spread of participants across Scotland, and explains what tests and scans each participant has undergone. The researchers also describe the clinical features of the cohort, such as age, sex, body mass index (BMI), what proportion smoke, and how their MS affects them in terms of physical disability, fatigue, mood and cognition (thinking, learning and memory). The researchers show that the characteristics of the FutureMS cohort mirror those of the Scottish population of people with MS as a whole – this is really important because it means that research findings are likely to be applicable to the wider group of patients. The FutureMS cohort is the largest study of its kind in the world, as far as we know, and it has tremendous potential to yield useful findings that will benefit people with MS.
Kearns PKA, Martin SJ, Chang J, Meijboom R, York EN, Chen Y, Weaver C, Stenson A, Hafezi K, Thomson S, Freyer E, Murphy L, Harroud A, Foley P, Hunt D, McLeod M, O'Riordan J, Carod-Artal FJ, MacDougall NJJ, Baranzini SE, Waldman AD, Connick P, Chandran S. BMJ Open2022;12:e058506. doi:10.1136/bmjopen-2021-058506
Rationale and design of the brain magnetic resonance imaging protocol for FutureMS: a longitudinal multi-centre study of newly diagnosed patients with relapsing-remitting multiple sclerosis in Scotland
This paper describes in detail the magnetic resonance imaging (MRI) scans that are an important part of the FutureMS study: how the researchers acquire, manage and store the data. In the first phase of FutureMS, participants underwent a brain scan soon after diagnosis and again 1 year later. To have these MRI findings available in several hundred people and at two different time points is an incredibly valuable resource for research. Our researchers can use the standard ways to measure changes in these brain scans, but also use the data to devise new ways to measure the effects of MS, for faster and more accurate diagnosis, monitoring of disease progression, and measuring the effects of drugs being tested in clinical trials.
Meijboom R, Wiseman SJ, York EN, Bastin ME, Valdés Hernández MC, Thrippleton MJ, Mollison D, White N, Kampaite A, Ng Kee Kwong KC, Rodriguez Gonzalez D, Job D, Weaver C, Kearns PKA, Connick P, Chandran S, Waldman AD. Wellcome Open Research. 2022;7. doi: 10.1101/2021.03.10.21253264
Quantitative magnetization transfer imaging in relapsing-remitting multiple sclerosis: a systematic review and meta-analysis
Brain scanning by magnetic resonance imaging (MRI) is hugely important in the diagnosis and monitoring of MS. One particular technique, called quantitative magnetization transfer (qMT) imaging, is often used in MS, as it is sensitive to the amount of myelin, a fatty substance that acts as an electrical ‘insulator’ around nerve cells, and can be lost in MS. This publication describes a systematic analysis of all the scientific literature on qMT imaging. The findings were that qMT imaging can be useful to measure brain changes in MS, but there is still room for improvement in the techniques used for analysis.
York EN, Thrippleton MJ, Meijboom R, Hunt DPJ, Waldman AD. Brain Communications. 2022;4(2):fcac088. doi: 10.1093/braincomms/fcac088
Longitudinal microstructural MRI markers of demyelination and neurodegeneration in early relapsing-remitting multiple sclerosis: Magnetisation transfer, water diffusion and g-ratio;
Here, researchers used the brain scan data from FutureMS participants to test advanced MRI techniques, and find out if they can provide more specific markers of brain changes in MS than those conventionally used. The researchers compared the brain scans taken at 1 year against those taken shortly after diagnosis, to look for changes that might be associated with the progression of MS during those 12 months. They identified several measures that changed during the one-year period in people with MS, which might be markers of disease progression. Further work is needed, but ultimately these advanced measures might help with understanding the brain changes that happen in MS, and how they can be monitored accurately over time.
York EN, Meijboom R, Thrippleton MJ, Bastin ME, Kampaite A, White N, Chandran S, Waldman AD. NeuroImage: Clinical. 2022;36:103228. doi: 10.1016/j.nicl.2022.103228
Rim lesions are demonstrated in early relapsing–remitting multiple sclerosis using 3 T-based susceptibility-weighted imaging in a multi-institutional setting
‘Rim lesions’ are particular features that can be identified on a brain scan. It has been previously suggested that the presence of these features is associated with ongoing disease processes in MS. In this study, the brain scans from 44 members of the FutureMS cohort were assessed for rim lesions. The results revealed that 27% of people had rim lesions approximately 1 year after diagnosis. However, there was no conclusive evidence regarding how the rim lesions were changing over time, or whether they associated with clinical features. The study emphasises the need for standardized criteria to define and validate rim lesions as a marker of chronic inflammation in MS.
Ng Kee Kwong KC, Mollison D, Meijboom R, York EN, Kampaite A, Martin SJ, Hunt DPJ, Thrippleton MJ, Chandran S, Waldman AD, FutureMS consortium. Neuroradiology. 2022;1-9. doi: 10.1007/s00234-022-02892-1
2021
MRI-derived g-ratio and lesion severity in newly diagnosed multiple sclerosis
Here, researchers investigated if nerve fibre damage and loss of myelin (the fatty substance that wraps around nerves and acts as an electrical ‘insulator’) are already present when a person is diagnosed with MS. The researchers studied the brain scans and blood test results of 73 FutureMS participants shortly after diagnosis. They found that in people whose brain scan results showed a greater loss of myelin, they tended to also find more of a protein called neurofilament in the blood. Neurofilament in blood is a marker of nerve fibre damage. This suggests that even at the time of diagnosis, MS patients already have myelin loss and nerve fibre damage. This study indicates the power of the FutureMS study, where blood test and brain scan results can be linked in the same individuals.
York EN, Martin SJ, Meijboom R, Thrippleton MJ, Bastin ME, Carter E, Overell J, Connick P, Chandran S, Waldman AD, Hunt DPJ, et al. Brain Communications. 2021;3(4):fcab249. doi: 10.1093/braincomms/fcab249
2020
Systematic review of prediction models in relapsing remitting multiple sclerosis
MS is hugely variable between people, and has always been difficult to predict how severe an individual’s disease course will be. This makes it difficult for people with MS to make life decisions and plan for the future, and it has long been a goal of researchers to develop a prediction tool. In this work, which was conducted early on in the FutureMS study, the researchers undertook a formal and structured assessment of 30 previously published MS prediction tools. The most commonly used predictor in these models was the initial level of disability, although brain imaging findings were also used. The authors found that most of the studies were at risk of bias, few were externally validated and none included an analysis of their impact. This means that most current prediction models for MS are not reliable enough for routine clinical use, emphasising the importance of the FutureMS study.