Trial Report Plasma Neurofilament Light Chain: A Potential Biomarker for Neurological Dysfunction in ME/CFS, 2024, Azcue et al

Full title:
Plasma Neurofilament Light Chain: A Potential Biomarker for Neurological Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disorder characterized by heterogeneous symptoms, which lack specific biomarkers for its diagnosis. This study aimed to investigate plasma neurofilament light chain (NfL) levels as a potential biomarker for ME/CFS and explore associations with cognitive, autonomic, and neuropathic symptoms. Here, 67 ME/CFS patients and 43 healthy controls (HCs) underwent comprehensive assessments, including neuropsychological evaluation, autonomic nervous system (ANS) testing, and plasma NfL level analysis. ME/CFS patients exhibited significantly higher plasma NfL levels compared to HC (F = 4.30, p < 0.05). Correlations were observed between NfL levels and cognitive impairment, particularly in visuospatial perception (r = −0.42; p ≤ 0.001), verbal memory (r = −0.35, p ≤ 0.005), and visual memory (r = −0.26; p < 0.05) in ME/CFS. Additionally, higher NfL levels were associated with worsened autonomic dysfunction in these patients, specifically in parasympathetic function (F = 9.48, p ≤ 0.003). In ME/CFS patients, NfL levels explained up to 17.2% of the results in cognitive tests. Unlike ME/CFS, in HC, NfL levels did not predict cognitive performance. Elevated plasma NfL levels in ME/CFS patients reflect neuroaxonal damage, contributing to cognitive dysfunction and autonomic impairment. These findings support the potential role of NfL as a biomarker for neurological dysfunction in ME/CFS. Further research is warranted to elucidate underlying mechanisms and clinical implications.

https://www.mdpi.com/2227-9059/12/7/1539

 

Not the first time NFL is appearing. Here is a link to a thread which includes links to several studies in LC and ME/CFS that find abnormalities in NFL. GFAP was also abnormal in the study by den Dunnen.

I think we might now really need to have a large and well conducted study on this topic in LC and ME/CFS, which also looks at variability in healthy controls including deconditioned controls.

I don't remember seeing it in the intramural study, but will have a look what was measured there.

 

I hope there will be a follow up that controls for PEM and/or time of onset and/or time since latest relapse etc. in some way.

I have argued with neurologists (without success) for years saying that any lack of signal in terms of classical biomarkers for neurodegeneration could be a timing issue, at least to a certain degree.

I have not talked to a single neurologist that had any clue about the kinetics of any of these biomarkers, so there is a chance they have missed it in some way. I doubt ME/CFS is a classical neurodegenerative disease, but that doesn’t mean there is no neurodegeneration.

 

These look like the main results:

 

Lightly peer-reviewed.

Submission received: 30 May 2024 /
Revised: 1 July 2024 /
Accepted: 5 July 2024 /
Published: 11 July 2024


Let’s say reviewers had 3 weeks to review. That would mean authors had maybe 5 days to make corrections and resubmit.

 

So I quickly looked at the intramural study again and the GFAP levels of pwME are somewhat elevated compared to healthy controls. The results are not statistically significant but that may be another issue. In fact @SNT Gatchaman had already discussed this problem with GFAP in the intramural study in this comment on the basis of one of the reviewers thinking it was an elevation that was worthy of being mentioned.