Predicting worsening

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To those familiar to the blog they will know what neurofilament is but simply put is is a structural protein only found inside nerves. So if you can detect it in biological fluids it says a nerve has got damaged. This study says neurofilament levels in blood predict a worse course. This is abit NSS because if disability is a product of previous nerve damage, then if you can measure markers of nerve damage in the blood then this cause will play out over time and disability or worsening will subsequently occur. However perhaps the surprise is that there is no link to MRI or OCT. Magnetic resonance imaging MRI) is a tool to measure brain changes. There are many many different sequences that can be measured and there is no doubt it is useful to measure lesion formation, but other measures such as atrophy have remained experimental/research rather than mainstream clinical practise. In some cases this is because they have no tangiable correlate with single entities of biology as such atrophy is a balance of shrinkage (due to nerve loss) and swelling due to inflammation, scarring etc. The other outcome is OCT and there are many, many papers linking progression to changes in OCT. Optical coherence tomography is a measure of the thickness of the retina in the eye. As nerves are lost in the visual pathway the nerves in the retina drop out and the retinal thins. So it has a correlate because if you have nerve damage throughout the nervous system you may see damage to the visual system. However if the damage is occuring in places that have no connections to the visual system then there is unlikely to be changes in the retina and so there will be no correlation with disability. Neurofilament is used routinely in our clinical practise but that is not the case for all practises. However it too has its issues, we assume neurofilament light is a marker of nerve damage but is ths what drives and measures progression. I would say not really because the vast majority of the neurofilament comes from damage caused by attacks and little comes from the slow-burning MS. I say this because of the results from natalizumab. This shuts down lession formation and this has a massive impact on neurofilament detection of the blood, so it is largely a marker of acute damage. This damgae may occur in places you are not looking at such as the spinal cord verses a brain scan or the lesions may be too small for the MRI to see.

Brune S et al. Serum neurofilament light chain concentration predicts disease worsening in multiple sclerosis. Mult Scler. 2022 Jun 4:13524585221097296. doi: 10.1177/13524585221097296

Background: Serum neurofilament light (sNfL) chain is a promising biomarker reflecting neuro-axonal injury in multiple sclerosis (MS). However, the ability of sNfL to predict outcomes in real-world MS cohorts requires further validation.

Objective: The aim of the study is to investigate the associations of sNfL concentration, magnetic resonance imaging (MRI) and retinal optical coherence tomography (OCT) markers with disease worsening in a longitudinal European multicentre MS cohort.

Methods: MS patients (n = 309) were prospectively enrolled at four centres and re-examined after 2 years (n = 226). NfL concentration was measured by single molecule array assay in serum. The patients’ phenotypes were thoroughly characterized with clinical examination, retinal OCT and MRI brain scans. The primary outcome was disease worsening at median 2-year follow-up.

Results: Patients with high sNfL concentrations (⩾8 pg/mL) at baseline had increased risk of disease worsening at median 2-year follow-up (odds ratio (95% confidence interval) = 2.8 (1.5-5.3), p = 0.001). We found no significant associations of MRI or OCT measures at baseline with risk of disease worsening.

Conclusion: Serum NfL concentration was the only factor associated with disease worsening, indicating that sNfL is a useful biomarker in MS that might be relevant in a clinical setting.

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MouseDoctor

1 comment

  • Really interesting post MD – thanks.
    If the biological measures all have their limitations then do the simply physical tests such as the 25m timed walk provide a more reliable measure of deterioration, or am I correct that there simply are no reliable means available.

    Stay well, and everyone else, in todays heat.

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