Neurofilament Light Chain and Its Role in Unlocking Prognosis
Multiple Sclerosis (MS) is often referred to as a “snowflake” disease because it affects each person differently, and likewise treatment is highly individualized. Just like snowflakes, each case of MS is unique. Since the disease course of MS varies drastically from person to person, prognostication is difficult. There is a clear desire among neurologists and patients alike for additional tools in the neurology toolkit for assessing prognosis.
When I was first diagnosed, I longed for a crystal ball that could offer me a glimpse into the future of my disease course. On the one hand, the fact that my first MS attack was Optic Neuritis is generally considered to be a good sign for a less aggressive disease course. On the other hand, the result of my spinal tap was alarming. I had a whopping 13 cerebrospinal fluid (CSF)-specific oligoclonal bands (2 or more is considered a positive test outcome for MS). I read a lot of medical literature. I just can’t help myself. I’m a nerd through and through and I just love to research things to death. This research led me to a study which concluded that a low number or absence of CSF-specific oligoclonal bands at diagnosis may predict a better prognosis, but also concluded that this remains an insensitive prognostic indicator that should not be used to influence treatment decisions. Over the course of the last two and a half years, I’ve settled down a bit and don’t spend as much of my time fretting over the future of my disease course, but I’d be lying if I told you that I wouldn’t still love a glimpse into that particular crystal ball.
My neurologist and one of his colleagues recently published a narrative review of the research regarding the use of Neurofilament Light Chain (NfL) as a prognostic biomarker, which served as inspiration for this blog post. You can read their article here: https://practicalneurology.com/articles/2024-mar/the-prognostic-utility-of-neurofilament-light-chain-in-multiple-sclerosis-a-narrative-review
What is Neurofilament Light Chain?
NfL is a protein component of the neuronal cytoskeleton. Think of the neuronal cytoskeleton like scaffolding that provides structure to the axons of our nerve cells, and think of NfL as part of the building materials that make up this scaffolding. It is released into the CSF and, to a lesser extent, the bloodstream when nerve cells are degenerating, such as when a demyelinating lesion forms in a person living with MS. Think of this like a wrecking ball smashing into the scaffolding and scattering debris, including those NfL building materials, everywhere. Elevated levels of NfL in the CSF or blood are associated with increased disease activity in MS.
MS attacks are not the only cause of NfL in the CSF and blood. Other neurological diseases, such as Alzheimer’s disease, Parkinson’s disease, and amoytrophic lateral sclerosis (ALS), as well as traumatic brain injuries and strokes are also known to contribute to NfL being present in higher concentrations in the CSF and blood. Basically, anything that causes damage to the scaffolding of the nerve cells can present with an elevation of NfL levels in the CSF and blood. Additionally, NfL in the CSF and blood is known to increase with age. NfL levels must be interpreted in the context of a patient’s overall health, medical history, age, and symptoms. As a result, elevated NfL levels alone cannot provide a definitive diagnosis of MS and it is unlikely to ever serve such a role in diagnosis. Elevated NfL levels can, however, serve as a biomarker of neuronal damage. This biomarker signals the need for further investigation into the neuronal health of the patient. In other words, an NfL blood test won’t tell us anything about what particular wrecking ball was smashed up against the scaffolding of the patient’s nerve cells, but it will tell us that it is happening.
What Does Neurofilament Light Chain Have to do with Assessing Prognosis in MS?
The regular monitoring of NfL levels in the blood could potentially be used to monitor individuals at highest risk for developing neurological disease. For example, those closely related to someone living with MS are at a known increased risk of developing MS. Measuring their blood levels of NfL could be used as an early warning system. An increase in NfL levels in the blood could serve as a trigger for requisitioning an MRI. This may allow for MS to be diagnosed and treated while it is still at a subclinical stage (i.e., before symptoms rear their ugly heads). Why is this exciting? Well, because research shows us that early intervention matters in MS. An MS attack is brain damage, and the more brain damage that is allowed to accrue, the greater the likelihood of permanent disability.
The regular monitoring of NfL levels in the blood of people living with MS could potentially be used to track disease progression and assess treatment response. There’s even the potential that monitoring of NfL levels in the blood could reduce reliance on MRI scans in the future. Rather than requiring all people living with MS to take an annual trip to their local MRI department, we could instead replace this with regular blood testing for those with relatively quiet disease, and use MRI when NfL levels are elevated. If NfL levels skyrocket in an MS patient, this is likely evidence of new disease activity unless there is another known cause, such as traumatic brain injury. Monitoring NfL blood levels likely would not replace reliance on MRI scans entirely, but it could mean less frequent routine monitoring by MRI. This would be welcome news for my fellow MS warriors that suffer from claustrophobia. It would also be welcome news to the public healthcare system, as MRI scans are costly. If blood testing could reliably identify those MS patients with more active disease, this could result in better treatment and a better allocation of more costly resources.
Measuring NfL levels in the blood could also offer neurologists earlier insights into the effectiveness of a patient’s Disease Modifying Therapy (DMT). Rather than the current wait and see approach that relies on additional lesions and/or clinical symptoms to arise in order to make the judgment that a particular DMT isn’t having the desired effect of slowing down disease course, a neurologist may measure changes in the NfL concentrations present in the patient’s blood to determine whether the DMT is slowing or halting disease progression sufficiently. If a DMT does not result in lowered NfL concentration in a patient’s blood, the neurologist may recommend a change in DMT before any further lesion-load is incurred.
I Have MS and I Haven’t Been Tested for Neurofilament Light Chain, What Gives?
While there is evidence that measurement of blood NfL levels in at risk populations can help to identify those likely to develop MS as early as 6 years before a clinical attack, and while there is evidence that it can be used to accurately predict relapses or subclinical disease activity in MS patients, the research is still at an early stage and we have not yet reached the point of blood NfL levels playing a diagnostic or prognostic role in routine MS care. Several factors hinder widespread adoption of using this biomarker in routine MS care. First, testing for NfL levels in the blood is expensive and not widely available at this time. The machinery needed to measure NfL in the blood is currently only available at a select number of research institutions. Siemens is currently working on this technology for more wide-spread usage. Additionally, testing protocols need to be standardized and universally recognized reference data needs to be established through further population level studies. Improvements in testing protocols must factor in the need for NfL testing to be cost-effective and accessible. Continued research in this area aims to address these obstacles with the aim of integrating NfL measurement into routine MS care. My neurologist and his colleague concluded: “Despite a need for further studies, the future of NfL as a prognostic marker for surveillance of disease activity and treatment response is bright, and presents an exciting, objective, and easily obtainable method of providing personalized management for people with MS”.
Did you know that MS Canada has been funding medical research into MS since 1949? Did you know that MS Canada is now, along with its related MS Scientific Research Foundation, the single largest funder of MS research in Canada? MS Canada directly funds the type of research that I’ve described above, with a view to improving the lives of people living with MS. You can support this important research and many other initiatives that directly benefit people living with MS by donating to my MS Walk fundraising drive. I hope that you will once again generously support me in this year’s campaign, and I appreciate each and every one of you who has supported me to date. To donate: https://msspwalk.donordrive.com/index.cfm?fuseaction=donorDrive.participant&participantID=41037
