Multiple Sclerosis International

Review Article

Cerebrospinal Fluid and Blood Biomarkers of Neuroaxonal Damage in Multiple Sclerosis

Table 1

Neurofilament subunits in the cerebrospinal fluid (CSF) and blood of patients with multiple sclerosis (MS) and/or clinically isolated syndrome suggestive of MS (CIS).


Biomarker (subtype)	Body fluid	Immunoassay	Number of patients	Main findings	REF

NF-L (cytoplasmic)	CSF	ELISA	60 MS (RR)	RR ↑↑ HCo	[61]
	CSF	Dot-blot	35 MS (RR/SP/PP)	MS ↑↑ OIND or NIND, PP/SP ↑↑ RR	[63]
	CSF	ELISA	66 MS (RR/SP)	RR/SP ↑↑ HCo	[64]
	CSF	ELISA	99 MS (RR/SP/PP/PR)	RR/SP/PP ↑↑ NHCo, SP the highest	[65]
	CSF	ELISA	51 MS (RR/SP/PP)	not detected	[66]
	CSF	ELISA	47 MS	MS ↑↑ healthy siblings or HCo	[67]
	CSF	ELISA	76 MS (RR/SP/PP) + 38 CIS	CIS+MS ↑↑ NIND+OIND + NHCo	[54]
	CSF	ELISA	5 MS (RR)	MS ↑↑ NHCo	[68]

NF-M (cytoplasmic)	CSF/PL/SE	not investigated	—	—	—

NF-H (cytoplasmic)	CSF	ELISA	38 MS (RR) + 52 CIS	NF-H^SM135 in CIS ↑↑ NHCo	[25]
	CSF	ELISA	41 ON	NF-H^SM134 and NF-H^SM134/SM135 in ON ↑↑ OND	[69]
	CSF	ELISA	51 MS (RR/SP/PP)	NF-H^SM135 RR ↔ SP ↔ PP	[66]
	CSF	ELISA	34 MS (RR/SP/PP)	NF-H^SM134 in PP/SP ↑↑ RR, NF-H^SM135 in SP/PP ↑↑ RR	[62]
	CSF	ECL	95 MS	MS ↑↑ NHCo	[23]
	CSF	ELISA	24 MS (RR/SP/PP)	NF-H^SM135 in SP ↑ RR	[70]
	PL	ELISA	18 ON	NF-H^SM135 in ON ↑↑ HCo	[71]
	CSF	ELISA	34 MS (RR)	NF-H^SM135 in MS ↑↑ NHCo	[72]
	CSF	ELISA	76 MS (RR/SP/PP) + 38 CIS	NF-H^SM135 in MS+CIS ↑↑ NHCo + NIND + OIND	[54]

REF: reference; NF-L: neurofilament-light chain; NF-M: neurofilament-intermediate chain; NF-H: neurofilament-heavy chain; PL: plasma; SE: serum; ELISA: Enzyme-Linked Immunosorbent Assay; ECL: Electrochemiluminescence-based solid-phase sandwich immunoassay; RR: relapsing-remitting MS; SP: secondary-progressive MS; PP: primary-progressive MS; ON: optic neuritis; NF-H^SM135: NF-H phosphorylated form; NF-H^SM134: NF-H hyperphosphorylated form; ↑↑ significantly higher than; ↑ higher than; ↔ no difference between; HCo: healthy controls; OIND: other inflammatory neurological diseases; NIND: noninflammatory neurological disorders; NHCo: neurologically healthy controls; OND: other neurological diseases.