Chapter 9 Impact paragraph
9.1 How will the findings impact future research?
The brain has gained a lot of attention in MS research and the spinal cord lagged behind, due to ongoing uncertainty of its clinical and therapeutic relevance, the challenges of MRI spinal cord imaging and the impact on imaging time and costs. Now, growing evidence confirms the importance of spinal cord involvement in MS [316] and research on the topic is expanding. The hope is that this will lead to spinal cord outcomes to be included in future medication trials. Also, in this thesis we saw that the registration of spinal cord follow-up data in registries is much more limited compared to brain data, posing challenges for retrospective observational research. On the wishlist, and what we advocate in this thesis, is: (i) spinal cord outcomes to be included in randomized-controlled trials in MS, (ii) more prospective observational studies including spinal cord imaging combined with (iii) MS registries encouraging to improve registration of data on spinal cord imaging (not only lesion data, but also raw images and details on image acquisition parameters), as real-world data stays a crucial source of data to answer important questions for MS clinical practice.
This thesis focused on the differences between spinal cord and brain pathology in MS and whether the differences between these CNS regions result in variations in the response to disease-modifying treatment. The main finding is that, while disease-modifying treatment in general seems to inhibit spinal cord lesion formation, that the added value of high-efficacy therapy with regard to spinal cord lesions is not as self-evident. Contributing to this are likely several important differences between spinal cord and brain — anatomical, vascular, immunological, and in terms of barrier functions. Hopefully, the results from this thesis can be seen as a plea to further explore these differences in more depth, in order to ultimately be better equipped to personalize treatment in MS patients with more cord involvement and optimize follow-up imaging regimens.
The retrospective studies and literature reviews from this thesis led to the grant application for the MSpine study in 2023 and which was approved by Nationaal MS fonds. The first patient was included in August 2024 and data collection is planned to be complete by 2028. In this prospective study the whole spinal cord (as well as routine brain MRI) is scanned yearly in the first 3 years after starting a first DMT, in addition to, clinical parameters, blood-biomarkers and CSF. The goal is to assess the incidence of asymptomatic spinal cord lesions in patients commencing treatment. It will be assessed how often disease activity is solely proven by spinal cord MRI. A secondary objective is to identify patient groups predisposed to developing new spinal cord lesions during follow-up in early disease.
9.2 What potential influence might the findings have on future clinical practice?
In the outpatient clinic it is not seldom that a patient asks, when the follow-up brain MRI is being ordered, “Why are we not scanning my spinal cord as well? I have had lesions there before”. This question is quite hard to answer with the limited evidence on asymptomatic cord lesions and on the effect of therapy on spinal cord lesion formation.
In the current international consensus guidelines [20], spinal cord MRI is not routinely recommended to detect subclinical activity and is mostly only scanned at follow-up in case of cord-related symptoms, unexplained disability progression or when a switch of treatment is considered. In the MS guidelines from the Dutch neurology association [317] spinal cord MRI at follow-up is only considered when there are cord-related symptoms.
The findings from this thesis support that what we know on how lesions behave in the brain and the effectiveness of DMTs in preventing new brain lesions cannot be simply extrapolated to the spinal cord. The data from the local cohort and from the MSBase combined with data in literature on asymptomatic lesions seem to provide arguments that at least annual follow-up in the first 2-3 years is arguable. Hopefully, with the data from the MSpine, we can consolidate this and additionally find markers to help us identify patients at risk of more spinal cord involvement. This can aid in the efficient use of MRI scanning resources in the follow-up of our MS patients. To give a rough impression of what kind of costs we are talking about: In the Netherlands there are approximately 37.500 MS patients, if you add one spinal cord MRI (~€450 in the Netherlands) to the follow-up for every patient, this costs almost 17 million euros. Therefore, recommendations in guidelines need to be considered carefully and this makes the collection of more evidence of importance. Finally, when we know more about the characteristics of the group of patients with more cord involvement, this can potentially also pave the way for studies to investigate what treatment approach would best benefit this subpopulation.
9.3 In what way is the target audience involved in and informed of the results of this research?
Chapter 2 to 7 have all been published in an open-access peer-reviewed scientific journal, which makes these works accessible not only to the scientific community but everyone. Additionally, this complete thesis will be published as an interactive thesis on https://spinalcordinms.nl. The code pipelines for the analyses for the studies in this thesis are available on GitHub (https://github.com/danielkreiter). Findings from the different studies within this thesis have been presented on different local (Zuyderland / Maastricht UMC+), national (Dutch Association of Neurology science days & Dutch national MS foundation MS day and sponsor day) and European conferences (European Association of Neurology congress). Background information on the MSpine study for patients is available on the website of the Dutch national MS foundation (Nationaal MS fonds https://nationaalmsfonds.nl/ruggenmerg-mri-monitoring-bij-ms/). On the events where our research and ambitions were presented for patients, it was really noticeable that this topic also lives among patients living with MS, which provides important additional motivation to continue this research line.