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] |
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| 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] |
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| 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] |
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| NF-L | CSF | RRMS (n = 47) | MS > controls | — | [24] |
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| NF-L | CSF | CDMS (n = 47) | MS > controls | — | [25] |
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| 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] |
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| 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] |
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| 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] |
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| NF-H | CSF | CIS (n = 52), RRMS (n = 38) | CIS > controls. ↑ acute relapse. | Correlated with EDSS for CIS and RRMS. | [28] |
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| 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.