Charcot-Marie-Tooth Disease Severity Indicated by Plasma Neurofilament Concentration

tubes of blood with platelets
tubes of blood with platelets
The measurement may provide a dynamic measure of axonal damage in a disease in which neuropathy is the only neurologic manifestation.

Raised plasma neurofilament light chain (NfL) concentration has promise as a sensitive biomarker for disease activity in and for the detection of peripheral axonal damage in Charcot-Marie-Tooth disease (CMT), according to study findings published Neurology.

Over a 1-year period, investigators obtained blood samples from patients with CMT (n=75) and compared these samples with samples collected from 67 age-matched healthy controls. The Rasch modified CMT Examination and neuropathy scores were used to measure disease severity and a Simoa assay was used to quantify plasma Nfl concentration.

Patients with CMT had significantly higher plasma Nfl concentrations than healthy controls (median 26.0 pg/mL vs median 14.6 pg/mL, respectively; P <.0001). Higher plasma Nfl concentrations were associated with disease severity based on the Rasch modified CMT examination (r = 0.43, P <.0001) and neuropathy (r = 0.37, P =.044) scores. Investigators found that the differences in plasma Nfl concentrations were sustained based on genetic subtypes, with higher plasma Nfl concentrations being found in the CMT1A (P <.0001), SPTLC1 (P <.001), and GJB1 (P =.011) genes.

In addition, the investigators discovered that correlations between the plasma Nfl concentrations with age were more significant in the healthy controls (r = 0.70, P <.0001) than in patients with CMT (r = 0.28, P =.012). The investigators discovered no significant differences in plasma Nfl concentrations between patients with CMT (n=9, mean difference −1.07 pg/mL, 95% CI, −8.2-6.0 pg/mL; paired t test P =.74) or controls (n=13, mean difference +1.19 pg/mL, 95% CI, −0.45-2.8, P =.14) from baseline to 1 year.

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Although these findings do not demonstrate the diagnostic utility of plasma Nfl concentrations, levels of Nfl may “provide a dynamic measure of axonal damage and serve as a biomarker of disease activity…especially in the many conditions like CMT where neuropathy is the only neurologic manifestation with no CNS involvement…”


Sandelius Å, Zetterberg H, Blennow K, et al. Plasma neurofilament light chain concentration in the inherited peripheral neuropathies [published online January 10, 2018]. Neurology. doi:10.1212/WNL.0000000000004932