Neurofilament light chain in clinical practice and research Flashcards
Describe the characteristics of Multiple Sclerosis (MS).
- Disease of the central nervous system, which is auto-immune mediated.
- It has two stages → inflammatory (caused by lymphocytes) and neurodegenerative (caused by microgial cells)
What cells are associated with the acute phase of MS and what do these cells cause?
B- and T-cells and macrophages, they cause inflammation.
What cells are associated with the chronic phase of MS and what do these cells cause?
Microglial cells that cause neurodegeneration
What are clinical presentations of MS?
- Subacute neurological dysfunction
- Dependent on lesion location
- Dysfunction lasting weeks, (partial) recovery afterward
- Accumulation of disability
For MS, there are different phenotypes such as: clinically isolated syndrome (CIS), relapsing remitting (RRMS), secondary progressive (SPMS) and primary progressive (PPMS).
Describe these different phenotypes.
- Clinically isolated syndrome (CIS) → a first episode of neurologic symptoms that lasts at least 24 hours and is caused by inflammation or demyelination.
- Relapsing remitting (RRMS) → a type of MS where you have relapses (worsening of symptoms) followed by recovery. The disability doesn’t get worse between relapses but after each relapse it can end up worse then before.
- Secondary progressive (SPMS) → a stage of MS which comes after relapsing remitting MS for many people. Here, the disability gets steadily worse and relapses are less likely to occur.
- Primary progressive (PPMS) → from the first (i.e. primary) symptoms, symptoms gets progressively worse.
For the diagnosis of MS, two criteria are used:
- dissemination in time
- dissemination in space
What is meant by this?
- Dissemination in time → MS-like neurologica damage that is occuring at multipe points in time
- Dissemination in space → the development of lesions in distinct anatomic locations withing the central nervous system, indicating a multifocal process.
Thus, these two criteria are proof of MS-like neurological damage at different places, at different times.
Instead of using the McDonald criteria for MS, what else can be used to diagnose MS?
By visualizing and measuring oligocloncal bands in CSF
According to the McDonald criteria, dissemination in space can be measured by visualizing bright lesions in 2 or more locations. What locations?
- Periventricular
- Cortical/Juxtacortical
- Infratentorial
- Spinal cord
What blood-based biomarker has recently been identified to aid in the diagnosis, prognosis and monitoring of treatments of MS?
Neurofilament light chain
What is neurofilament light chain (NfL)?
Axons are made up of neurofilaments. These neurofilaments are part of the axonal cytoskeleton and consist of different subunits (see picture). Neurofilament light chain is a specific neurofilament that is known to be released due to neurodegeneration associated with MS.
How can neurofilament light chain be used for the diagnosis of MS?
During neurodegeneration there is of course axonal injury. Axonal injury causes the release of these neurofilament that end up in the CSF and blood. With the use of neurofilament assays, NfL can be detected and used for the diagnosis of MS.
How can neurofilament light chain (NfL) be detected in the blood?
- Use an antibody that is able to bind to NfL.
- Capture the antibody on beads
- Add the sample (i.e. blood) and use the antibodies on the beads to detect NfL
- Add a solution to microwells (in every well 1-2 beads)
- Add oil to form liquid-tight seal
- Take fluorescent image of the microwells using a microscope
Name three things that are associated with NfL.
- Disease activity
- Expanded Disability Status Scale (EDSS)
- MRI lesion activity
Why is NfL not a perfect biomarker?
- NfL strongly rises with age
- Not specific to MS
- Not specific to central nervous system
- NfL influenced by BMI and kidney disease
- NfL normalizes slowly
For what other settings can NfL be used?
- Dementia
- CVA
- Intensive care
