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Multicenter Study
. 2024 Jan;39(1):209-214.
doi: 10.1002/mds.29680. Epub 2023 Dec 6.

Serum Neurofilament Light Chain in Replication Factor Complex Subunit 1 CANVAS and Disease Spectrum

Ilaria Quartesan  1   2 , Elisa Vegezzi  1   2 , Riccardo Currò  1   3 , Amanda Heslegrave  4   5 , Chiara Pisciotta  6 , Pablo Iruzubieta  7 , Alessandro Salvalaggio  8 , Gorka Fernández-Eulate  9 , Natalia Dominik  3 , Bianca Rugginini  1 , Arianna Manini  3   10 , Elena Abati  3   11 , Stefano Facchini  2 , Katarina Manso  12 , Ines Albajar  7 , Rhiannon Laban  5 , Alexander M Rossor  3 , Anna Pichiecchio  1   2 , Giuseppe Cosentino  1   2 , Paola Saveri  6 , Ettore Salsano  6 , Francesca Andreetta  6 , Enza M Valente  1   2 , Henrik Zetterberg  4   5   12   13   14   15 , Paola Giunti  16 , Tanya Stojkovic  9 , Chiara Briani  8 , Adolfo López de Munain  7 , Davide Pareyson  6 , Mary M Reilly  3 , Henry Houlden  3 , Cristina Tassorelli  1   2 , Andrea Cortese  1   3
Affiliations
Multicenter Study

Serum Neurofilament Light Chain in Replication Factor Complex Subunit 1 CANVAS and Disease Spectrum

Ilaria Quartesan et al. Mov Disord. 2024 Jan.

Abstract

Background: Biallelic intronic AAGGG repeat expansions in the replication factor complex subunit 1 (RFC1) gene were identified as the leading cause of cerebellar ataxia, neuropathy, vestibular areflexia syndrome. Patients exhibit significant clinical heterogeneity and variable disease course, but no potential biomarker has been identified to date.

Objectives: In this multicenter cross-sectional study, we aimed to evaluate neurofilament light (NfL) chain serum levels in a cohort of RFC1 disease patients and to correlate NfL serum concentrations with clinical phenotype and disease severity.

Methods: Sixty-one patients with genetically confirmed RFC1 disease and 48 healthy controls (HCs) were enrolled from six neurological centers. Serum NfL concentration was measured using the single molecule array assay technique.

Results: Serum NfL concentration was significantly higher in patients with RFC1 disease compared to age- and-sex-matched HCs (P < 0.0001). NfL level showed a moderate correlation with age in both HCs (r = 0.4353, P = 0.0020) and patients (r = 0.4092, P = 0.0011). Mean NfL concentration appeared to be significantly higher in patients with cerebellar involvement compared to patients without cerebellar dysfunction (27.88 vs. 21.84 pg/mL, P = 0.0081). The association between cerebellar involvement and NfL remained significant after controlling for age and sex (β = 0.260, P = 0.034).

Conclusions: Serum NfL levels are significantly higher in patients with RFC1 disease compared to HCs and correlate with cerebellar involvement. Longitudinal studies are warranted to assess its change over time.

Keywords: ataxia; biomarkers; cerebellar ataxia neuropathy vestibular areflexia syndrome; neurofilament light chain; replication factor complex subunit 1.

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Figures

FIG. 1
FIG. 1
(A) Increased serum NfL concentration in patients with RFC1 disease compared to healthy controls (HC). (B) Receiver operator curve of serum NfL concentration for detecting patients with RFC1 CANVAS and disease spectrum. (C) Correlation between serum NfL concentration and age in both patients carrying RFC1 expansions and HCs. (D) Increased serum NfL concentration in patients with cerebellar involvement compared to patients without cerebellar dysfunction. Both subgroups show higher concentrations compared to HCs. Line is at mean. Error bars: standard deviation. P‐value less than 0.05 is flagged with one star (*), P‐value less than 0.01 is flagged with two stars (**), and P‐value less than 0.001 is flagged with three stars (***). NfL: neurofilament light. CANVAS: cerebellar ataxia, neuropathy, vestibular areflexia syndrome. [Color figure can be viewed at wileyonlinelibrary.com]
See this image and copyright information in PMC

References

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