Neurofilament Proteins as Body Fluid Biomarkers of Neurodegeneration in Multiple Sclerosis

Table 1

Summary of studies assessing the utility of neurofilaments as biomarkers of axonal damage in patients with multiple sclerosis (MS) and clinically isolated syndrome (CIS).

Biomarker	Fluid	Study design	Observations	Associations with clinical measures	Ref.
NF-L	CSF	RRMS (𝑛=60); LP on trial initiation and 2 yr	78% patients showed ↑ at 0 or 2 yrs. Associated with recent relapse. No relation with age, gender, or disease duration.	EDSS; 0 yr (𝑟^2=0.27,𝑃<.05); 2 yr (𝑟^2=0.35,𝑃<.01)	[16]
NF-L	CSF	RRMS (𝑛=41), SPMS (𝑛=25), healthy (𝑛=50)	↑ mean level in all MS subtypes. Highest during acute relapse.	EDSS (ns)	[17]
NF-L	CSF	CIS (𝑛=38), RRMS (𝑛=42), SPMS (𝑛=28), PPMS (𝑛=6); diagnostic LP	MS/CIS > controls. ↑ NF-L associated with relapse, T2 lesion number, Gd enhancing lesions. ↑ in CIS that convert to RRMS.	EDSS (𝑟=0.192, 𝑃<.05)	[18]
NF-L	CSF	RRMS (𝑛=16), SP/PP MS (𝑛=18)	MS > controls	EDSS (𝑟=0.41, 𝑃<.05)	[23]
NF-L	CSF	RRMS (𝑛=47)	MS > controls	—	[24]
NF-L	CSF	CDMS (𝑛=47)	MS > controls	—	[25]
NF-L	CSF	RRMS (𝑛=65), SPMS (𝑛=10), PPMS (𝑛=20); LP on initiation. Followup at 5 and 14 yrs.	↑ NF-L associated with recent relapse; associated with 3-fold ↑ in risk of developing high MSSS; more likely to convert from RRMS to SPMS.	MSSS 14 yr (𝑟=0.3, 𝑃<.01)	[26, 27]
NF-H	CSF	CIS (𝑛=38), RRMS (𝑛=92), SPMS (𝑛=28), PPMS (𝑛=6); diagnostic LP	MS > controls. SP/PPMS > RRMS. ↑ levels at CIS do not predict conversion to RRMS. ↑ with relapse. Correlated to age.	EDSS (𝑟=0.253,𝑃<.01)	[18]
NF-H	CSF	RRMS (𝑛=11), SP/PPMS (𝑛=23); LP on trial initiation and 3 yr	SP/PPMS > RRMS.	EDSS 3 yr (ns trend)	[19]
NF-H	CSF	CIS (𝑛=52), RRMS (𝑛=38)	CIS > controls. ↑ acute relapse.	Correlated with EDSS for CIS and RRMS.	[28]
NF-H	Plasma	RRMS (𝑛=30)	Median levels RRMS > controls	—	[20]

Abbreviations: NF-L: neurofilament light; NF-H: neurofilament heavy; CSF: cerebrospinal fluid; RRMS: relapsing-remitting MS; SPMS: secondary progressive MS; PPMS: primary progressive MS; CDMS: clinically definite MS; LP: lumbar puncture; Gd: gadolinium; EDSS: expanded disability status scale; MSSS: multiple sclerosis severity scale; NS: nonsignificant; Ref: reference.