In my opinion, if the latter half of the 21st century in MS was defined by something it was the realization that neurofilament levels introduce clarity into individual disease courses that was not possible with clinical descriptors or MRI alone.
The days of wandering what your MS is going to be like in the future may well be over as new tools such as neurofilaments become more readily available.
This letter published in the Journal of Internal Medicine demonstrates that blood neurofilament levels followed-up by 13.5 years (on average 6.2 years) were associated with loss in cortical volume (surface of the brain) despite stable T1 lesion volumes (essentially areas of hypointensity on MRI brain scans in MS – please see slide below).
Previously, a limited analysis of the fingolimod data (Phase 3 study) demonstrated that the effect of fingolimod on lowering neurofilament levels captured 60% of its effect on brain volume loss, whilst active lesions only captured 45%.
Having said all of this, this evidence for blood neurofilaments is based on a group effect. In this letter the authors point out that “NfL levels were around 50 times higher in CSF compared with plasma (median plasma NfL levels [IQR]: 12.1 pg/mL [8.4–18.5], median CSF NfL levels [IQR]: 665 pg/mL [375.2–1347.2])“. Spot CSF NfL levels therefore remain the more informative test in deciphering who is highly active compared to blood neurofilaments. However, this may change as we learn more about individual fluctuations in blood neurofilament.
J Intern Med. 2021 Apr 19. doi: 10.1111/joim.13286. Online ahead of print.
Neurofilament light chain as a marker for cortical atrophy in multiple sclerosis without radiological signs of disease activity
Neuroﬁlament light chain (NfL) appears to reﬂect nerve-damaging inﬂammatory disease activity and neuroaxonal degeneration in multiple sclerosis (MS) . However, to what degree NfL can provide additional information not conveyed by magnetic resonance imaging (MRI) monitoring is less clear. Hence, it is still a matter of debate whether NfL mainly reﬂects ongoing focal neuroaxonal damage or whether it also can be used to assess diffuse, smouldering neurodegeneration for which both clinical MRI monitoring and conventional MRI monitoring have low sensitivity. Resolving this issue would help to understand the potential added value of assessing NfL in clinical practice and whether plasma NfL measurements can sub-stitute for more invasive CSF sampling. The objective of this study was to investigate the relationship between plasma and CSF NfL concentrations and imaging measures, as well as with volumetric changes in strategic brain structures, in a well-characterised incident MS cohort with long-term
Disclaimer: Please note that the opinions expressed here are those of the author NDG and do not reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust or Queen Mary University of London.