NfL in clinical practice

Question 1

What is Multiple Sclerosis (MS)?

Answer 1

• autoimmune disease
• traditionally seen as –> two-stage disease –> inflammatory (lymphocytes) + neurodegenerative (microglial cells)
• in schubs –> relapsing-remitting disease (accumulation of disease)
• potentially disabling disease of the brain and spinal cord (central nervous system)
• attack protective myelin sheaths - that covers nerve fibers –> causes communication problems between brain and the rest of body
• Eventually, disease can cause permanent damage or deterioration of nerves

Question 2

What is NfL?

Answer 2

• neurofilament light chain protein = NfL –> which provides a sensitive measurement of neuroaxonal damage, regardless of cause

Question 3

What are and what is the difference between
absolute values vs. relative values?

Answer 3

absolute value: intrinsic value without comparing to any other

relative value: value in comparison to others

Question 4

How is NfL applied in clinic?

Answer 4

• has multiple applications
• road is long - not specific to one disease
• absolute values not perfect
• correction song percentiles or Z-scores

Question 5

What is the pathogenic difference between the acute and the chronic phase in MS?

Answer 5

acute phase:
- inflammation
- B-cells
- T-cells
- Macrophages

chronic phase: (partial) recovery
- Neurodegenerative
- Microglial cells

Question 6

Phenotypes of MS

Answer 6

Clinically Isolated Syndrome (CIS)

Relapsing Remitting MS (RRMS)

Secondary Progressive MS (SPMS)

Primary Progressive (PPMS)

Question 7

What does the Secondary Progressive MS (SPMS) phenotype of MS entail?

Answer 7

Secondary Progressive MS (SPMS)
- initial relapse-remitting course (RRMS)
- progressive worsening of neurological function

Question 8

What does the Primary Progressive (PPMS) phenotype of MS entail?

Answer 8

Primary Progressive (PPMS)
- characterized by worsening neurologic function (accumulation of disability) from the onset of symptoms, without early relapses or remissions

Question 9

What does the Clinically Isolated Syndrome (CIS) phenotype of MS entail?

Answer 9

Clinically Isolated Syndrome (CIS)
- first episode of neurologic symptoms caused by inflammation and demyelination in the central nervous system (min. 24h)
- is characteristic of multiple sclerosis but does not yet meet the criteria for a diagnosis - because people with CIS may or may not go on to develop MS

Question 10

What does the Relapsing Remitting MS (RRMS)) phenotype of MS entail?

Answer 10

Relapsing Remitting MS (RRMS)
- most common disease course
- clearly defined attacks of new or increasing neurologic symptoms –> relapse followed by partial/complete remission

Question 11

All phenotypes can be active vs not active and with progression vs without progression. What does each mean?

Answer 11

• active –> with relapses and/or evidence of new MRI activity during a specified period of time
• non active
• with progression –> evidence of disability accumulation over time, with or without relapses or new MRI activity
• without progression

Question 12

What diagnostic criteria must be fulfilled for a MS diagnosis?

Answer 12

Dissemination in space –> bright lesions in 2 or more of the following locations
Dissemination in time –> at different points in time

Question 13

What does it mean when a person in OCB pos.?
How is OCB measured?

Answer 13

Oligoclonal bands (OCBs) are a type of protein that occurs in the cerebrospinal fluid (CSF). The presence of these immunoglobulins can indicate inflammation in the central nervous system (CNS), which can suggest that a person has multiple sclerosis (MS)

In the CSF

Question 14

What are the issues with using NfL as a biomarker for MS?

Answer 14

NfL
- rises strongly with age
- not specific to MS
- not specific to CNS (central nervous system)
- influenced by BMI
- influenced by kidney disease
- normalised only slowly

Question 15

Where is NfL also used as a biomarker?

Answer 15

• MS
• Dementia
• CVA (Cerebro Vasculair Accident)
• Intensive care (Covid)