VUB researchers Guy Nagels and Jeroen Van Schependom on the invisible impact of multiple sclerosis

Guy Nagels: “Multiple sclerosis is a disease of the central nervous system. Yes, some people experience motor impairments and may even need a wheelchair. But thanks to better treatments, that group has fortunately become smaller. What is far less visible are the cognitive problems. Around half of people with MS are affected by them, to a greater or lesser extent.” 

Those cognitive impairments are somewhat comparable to dementia, but more subtle and persistent: planning becomes harder, thinking slows down, mistakes happen more quickly. “And that can have a major impact on your work, your independence and your social life,” says Nagels. “What’s more, they are closely intertwined with two other invisible symptoms: fatigue and depression.”

Fatigue in MS is not just feeling tired. “It is disabling,” he stresses. “It completely drains people, and recovery takes a very long time. It is harder to grasp because you cannot see it, but it shapes the lives of many patients.”

MS is usually diagnosed only when clear neurological symptoms appear. But subtle signs may be present much earlier. Jeroen Van Schependom: “Fatigue or mild cognitive complaints are often not immediately linked to MS. In that sense, the disease is also invisible before the diagnosis.”

The diagnosis itself is based on a combination of a clinical consultation, neurological examination, MRI and sometimes additional tests such as neurophysiology or a lumbar puncture. Nagels: “MS can cause a wide range of symptoms. That is why the overall puzzle matters.”

When it comes to the cause, much remains uncertain. “We know MS is not contagious and not purely hereditary,” says Nagels. “It is a complex interaction between genetic susceptibility and environmental factors. We are learning more all the time, but we still do not know exactly why one person develops MS and another does not.”

The AIMS research group grew out of the Neurology Research Group led by Professor Sebastiaan Engelborghs and focuses on understanding brain function, both in healthy individuals and in neurological conditions such as MS and Alzheimer’s disease.

Van Schependom: “We start from one central question: how do our brain networks function? We no longer assume that one brain area serves one function. Instead, we see the brain as a set of dynamic networks that constantly communicate with each other.”

The group works along three research pillars. First, they aim to measure brain activity using EEG (electroencephalography) and MEG (magnetoencephalography). “These techniques allow us to detect very small electrical and magnetic signals,” Van Schependom explains. “We look at how stable the networks are, how well they communicate, and at the balance between excitation and inhibition — neurons that activate each other or, conversely, slow each other down.”
In MS, this balance is disrupted, which can for instance lead to difficulties in suppressing impulses.

In addition to neurophysiology, imaging plays a major role — which brings us to the second pillar. Nagels: “We want to use MRI scans as a biomarker. Can we predict how severe the disease will become on the basis of a single scan? At present, we cannot do that accurately enough at an individual level.”

That is why AIMS strongly invests in artificial intelligence. “But AI needs large amounts of data, and those data are spread across hospitals all over Europe,” says Nagels. “You cannot simply send them around because of privacy rules and GDPR.”

The solution is called federated learning, where the model travels but the data stay local. “This allows us to train AI models on thousands of MRI scans without sensitive data ever leaving hospital walls. That network is growing fast, even extending into Asia, where MS variants occur that share cognitive consequences but follow a different course.

The third pillar focuses on testing new treatment strategies. Alongside measuring and modelling, AIMS works on innovative therapies. Van Schependom: “We study cognitive and motor training, but also neurostimulation: very weak, targeted electrical signals to influence brain networks. To be clear, this is not electroconvulsive therapy; the currents are a thousand times weaker and far more precise.”

Repairing damage

The ambition? To stimulate recovery. In MS, myelin — the insulating layer around nerve fibres — is damaged. It can recover spontaneously, but often only partially. Nagels: “Pharmaceutical companies have tried to stimulate this repair with medication, but without success. That makes research into neurostimulation particularly exciting.”

For now, the team mainly tests in mouse models, but translating animal research to the clinic remains challenging. “MS does not exist in mice,” says Van Schependom. “We use models that mimic certain aspects, but never the full disease. That is why we always test across multiple models before moving to humans.”

Reading out the effects also differs greatly between mice and humans. “With mice, we can literally place brain tissue under a microscope. With people, obviously not,” Nagels explains. “That is where MRI comes back into play.”

With the arrival of the 7 Tesla MRI scanner at VUB-UMC, new doors are opening. “This ultra-high field strength allows us to study myelin and lesions in far greater detail,” says Nagels. “The radiology team is strongly committed to this, and we are now preparing new studies together with, among others, Sebastiaan Engelborghs and physicist Bert Raeymackers.”

Both Nagels and Van Schependom emphasise that the field is now on the brink of a new research phase. “With federated learning, new neurostimulation techniques and the 7 Tesla MRI, we are getting closer to what seemed impossible twenty years ago,” says Van Schependom. “We are still at the beginning, but the potential is huge.”
Nagels adds: “The ultimate goal? Not only to treat inflammation, but also to repair damage. To give people with MS a future in which not just the visible, but also the invisible becomes more manageable. Or even reversible.”