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. 2018 Feb 6;90(6):e518-e524.
doi: 10.1212/WNL.0000000000004932. Epub 2018 Jan 10.

Plasma neurofilament light chain concentration in the inherited peripheral neuropathies

Åsa Sandelius  1 , Henrik Zetterberg  1 , Kaj Blennow  1 , Rocco Adiutori  1 , Andrea Malaspina  1 , Matilde Laura  1 , Mary M Reilly  2 , Alexander M Rossor  1
Affiliations

Plasma neurofilament light chain concentration in the inherited peripheral neuropathies

Åsa Sandelius et al. Neurology. .

Abstract

Objective: To perform a cross-sectional study to determine whether plasma neurofilament light chain (NfL) concentration is elevated in patients with Charcot-Marie-Tooth disease (CMT) and if it correlates with disease severity.

Methods: Blood samples were collected from 75 patients with CMT and 67 age-matched healthy controls over a 1-year period. Disease severity was measured using the Rasch modified CMT Examination and neuropathy scores. Plasma NfL concentration was measured using an in-house-developed Simoa assay.

Results: Plasma NfL concentration was significantly higher in patients with CMT (median 26.0 pg/mL) compared to healthy controls (median 14.6 pg/mL, p < 0.0001) and correlated with disease severity as measured using the Rasch modified CMT examination (r = 0.43, p < 0.0001) and neuropathy (r = 0.37, p = 0.044) scores. Concentrations were also significantly higher when subdividing patients by genetic subtype (CMT1A, SPTLC1, and GJB1) or into demyelinating or axonal forms compared to healthy controls.

Conclusion: There are currently no validated blood biomarkers for peripheral neuropathy. The significantly raised plasma NfL concentration in patients with CMT and its correlation with disease severity suggest that plasma NfL holds promise as a biomarker of disease activity, not only for inherited neuropathies but for peripheral neuropathy in general.

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Figures

Figure 1
Figure 1. Plasma neurofilament light (NfL) concentration in Charcot-Marie-Tooth disease (CMT)
(A) Significantly increased plasma NfL concentration in patients with CMT (n = 75) compared to healthy controls (n = 67). (B) Significantly increased plasma NfL concentration in patients with more severe disease (weighted CMT examination score [CMTES] >10) vs milder CMT (weighted CMTES <10) and healthy controls. (C) Plasma NfL concentration for the 3 largest subgroups of CMT, CMT1A (n = 31), hereditary sensory neuropathy due to mutations in SPTLC1 (n = 20), and CMTX1 (n = 11).
Figure 2
Figure 2. Plasma neurofilament light (NfL) concentration and Charcot-Marie-Tooth disease (CMT) severity
(A) Significant correlation between disease severity as measured by the weighted CMT examination score (CMTES) and plasma NfL concentration. (B) Significant correlation between plasma NfL concentration and disease severity as measured by the weighted CMT neuropathy score (CMTNS). (C) Significant correlation between plasma NfL concentration and age, which is more pronounced for healthy controls.
Figure 3
Figure 3. Plasma neurofilament light (NfL) concentration as a diagnostic biomarker of Charcot-Marie-Tooth disease (CMT)
(A) The individual NfL concentration at baseline and after 1 year for all patients with CMT (n = 9) and healthy controls (n = 13). Above the bars is the individual change in weighted CMT over 1 year. There is no significant difference in plasma NfL concentration in either patients with CMT or healthy controls after 1 year. (B) Receiver operator curve of NfL concentration for detecting patients with peripheral neuropathy. AUC = area under the curve.
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