ECTRIMS 2025 | The association of plasma neurofilament light chain, neuroaxonal loss, and patient-reported outcomes

Neurofilament light chain is a small component of the neuron, which means that if the neuron is damaged, the neurofilament light chain is released first in the CSF and then from the CSF into the blood. So measuring the neurofilament in the blood means detecting axonal damage in the brain. This is a window of opportunity to study the correlates of neuroaxonal loss in MS with minimally invasive tests, because basically we can do the neurofilament using a very small quantity of blood. In that sense, we need to develop clinical measures that reflect disease mechanisms. Because if we want to develop medications that target disease mechanisms, we want also to have clinically meaningful changes. And this is not always the case. So for instance, we have been very good in reducing relapses, less so in patient-reported outcomes. So medications can sometimes reduce in an excellent way the number of relapses, the number of brain lesions that we know are highly correlated to the neurofilament, but they are not equally good in improving patient-reported outcomes such as fatigue or depression or poor sleep. And actually, these patient-reported outcomes based on our study might not be related to neuroaxonal loss. So they might be related, for instance, to other mechanisms of chronic inflammation in the brain or perhaps to a self-perception of the disease itself and of its symptoms. This, of course, makes things a little more complicated, but we hope that with the cooperation of new biomarkers, we will be able to shed further light on the mechanisms of patient-reported outcomes in MS.

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