Tuesday, 25 August 2015

Now you see and now you don't - Neurofilament predicts visual outcome

Mult Scler. 2015 Aug 17. pii: 1352458515599074. [Epub ahead of print]

Cerebrospinal fluid neurofilament light chain levels predict visual outcome after optic neuritis.

Modvig S, Degn M, Sander B, Horwitz H, Wanscher B, Sellebjerg F, Frederiksen JL



Optic neuritis is a good model for multiple sclerosis relapse, but currently no tests can accurately predict visual outcome.


The purpose of this study was to examine whether cerebrospinal fluid (CSF) biomarkers of tissue damage and remodelling (neurofilament light chain (NF-L), myelin basic protein, osteopontin and chitinase-3-like-1) predict visual outcome after optic neuritis.

We included 47 patients with optic neuritis as a first demyelinating episode. Patients underwent visual tests, optical coherence tomography (OCT), magnetic resonance imaging (MRI) and lumbar puncture. Biomarkers were measured in CSF by enzyme-linked immunosorbent assay (ELISA). Patients were followed up six months after onset and this included visual tests and OCT. Outcome measures were inter-ocular differences in low contrast visual acuity (LCVA), retinal nerve fibre layer (RNFL) and ganglion cell layer+inner plexiform layer (GC-IPL) thicknesses.

CSF NF-L levels at onset predicted inter-ocular differences in follow-up LCVA (β=13.8, p=0.0008), RNFL (β=5.6, p=0.0004) and GC-IPL (β=4.0, p=0.0008). The acute-phase GC-IPL thickness also predicted follow-up LCVA (β=12.9, p=0.0021 for NF-L, β=-1.1, p=0.0150 for GC-IPL). Complete/incomplete remission was determined based on LCVA from 30 healthy controls. NF-L had a positive predictive value of 91% and an area under the curve (AUC) of 0.79 for incomplete remission.

CSF NF-L is a promising biomarker of visual outcome after optic neuritis. This could aid neuroprotective/regenerative medical advancements.

So the key here is that there are no available tests (biological or imaging wise) which can predict visual outcome following optic neuritis at the time of onset of the disease. Jette Frederikesen's group suggest that CSF (cerebrospinal fluid) NF-L (light chain, heavy chain was not tested here but there is work in the literature suggesting similar outcomes) can predict this in 91% of cases. Equally, as the patients recover, the NF-L levels also dropped, providing proof-of-concept. What I find interesting is the relative load of NF-L in the CSF compartment following optic neuritis (see figures below, 10,000 ng/L is the top standard in the assay) - should we be worried?

Figure: Associations between baseline cerebrospinal fluid (CSF) neurofilament light chain (NF-L) levels and visual outcome parameters after optic neuritis (ON).Associations between CSF NF-L levels measured in the acute phase of optic neuritis and inter-ocular differences in visual outcome measures: (a) low contrast visual acuity (LCVA) function (b) retinal nerve fibre layer (RNFL) thickness and (c) ganglion cell layer+inner plexiform layer (GC-IPL) thickness. A high value on the y-axis thus indicates a poor clinical outcome and high degree of neuronal loss. Correlation coefficients (r=Spearman’s rho) and p-values as calculated by Spearman’s rank correlation analysis are given at the top of each panel.


  1. It could analyze the presence of neurofilament in CSF at intervals, such as MRI, or would only be used in analysis when outbreaks or when research for the diagnosis of MS?

    1. There is still a lot to be learned about neurofilaments. It has value as a bulk marker, so on average if your level is elevated through the year - this is probably not good. High baseline levels early on is also probably not good - this is what we demonstrate in our ECTRIMS 2015 abstract. We may be able to classify what are really bad relapses based on the scale of neurofilament release in the future, and also subclinical relapses - a step closer to NEDA and MS remission. As I've posted before our plan is to offer neurofilament analysis for clinical use, and push clinicians into thinking about neuroprotection in their patients.

    2. Oh yeah I get it. I remember about their previous publication about the possible neurofilament analysis of CSF in Barts. I commented on the blog with some residency in neurology students taking part of my routine care every 3 months ... I'll see if I comment with my neuro about it, she is the head teacher of neurology where I would be treatment ..It would be possible to send the CSF EM'ers from other countries?

    3. Yes I believe It would be possible to send the CSF from EM'ers (from Portuguese
      [esclerose múltipla] speaking countries :-) from other countries but SDG can confirm.

    4. yes, this should be possible as it's done for other tests


Please note that all comments are moderated and any personal or marketing-related submissions will not be shown.