Serum Neurofilament Light Chain in Pediatric Spinal Muscular Atrophy Patients and Healthy Children

Overview

Journal Ann Clin Transl Neurol

Specialty Neurology

Date 2021 Sep 5

PMID 34482646

Citations 30

Authors

Elisa Nitz

Martin Smitka

Jens Schallner

Katja Akgun

Tjalf Ziemssen

Maja von der Hagen

Victoria Tungler

Affiliations

Soon will be listed here.

Abstract

Objective: The aim of this study was to evaluate neurofilament light chain as blood biomarker for disease activity in children and adolescents with different types of spinal muscular atrophy (SMA) and establish pediatric reference values.

Methods: We measured neurofilament light chain levels in serum (sNfL) and cerebral spinal fluid (cNfL) of 18 children with SMA and varying numbers of SMN2 copies receiving nusinersen by single-molecule array (SiMoA) assay and analyzed correlations with baseline characteristics and motor development. Additionally, we examined sNfL in 97 neurologically healthy children.

Results: Median sNfL levels in treatment-naïve SMA patients with 2 SMN2 copies are higher than in those with >2 SMN2 copies (P < 0.001) as well as age-matched controls (P = 0.010) and decline during treatment. The median sNfL concentration of healthy controls is 4.73 pg/mL with no differences in sex (P = 0.486) but age (P < 0.001). In all children with SMA, sNfL levels correlate strongly with cNfL levels (r = 0.7, P < 0.001). In children with SMA and 2 SMN2 copies, sNfL values correlate with motor function (r = -0.6, P = 0.134), in contrast to older SMA children with >2 SMN2 copies (r = -0.1, P = 0.744).

Interpretation: Reference sNfL values of our large pediatric control cohort may be applied for future studies. Strong correlations between sNfL and cNfL together with motor function suggest that sNfL may be a suitable biomarker for disease activity in children with 2 SMN2 copies and those with >2 SMN2 copies within their initial stages during early childhood.

Citing Articles

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PMID: 39946662 PMC: 11837849. DOI: 10.1212/WNL.0000000000213371.

Neurofilament light chain (Nf-L) in cerebrospinal fluid and serum as a potential biomarker in the differential diagnosis of neurological diseases in cattle.

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Shi T, Zhou Z, Xiang T, Suo Y, Shi X, Li Y J Neurol. 2024; 272(1):19.

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Maretina M, Koroleva V, Shchugareva L, Glotov A, Kiselev A Biomedicines. 2024; 12(11).

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High Expression of SMN circ4-2b-3 in SMA I Children Treated with Nusinersen is Associated with Improved Motor Outcomes.

Guerra M, Marini A, Pagliarini V, Pitolli C, Coratti G, Bonvissuto D Mol Neurobiol. 2024; .

PMID: 39592557 DOI: 10.1007/s12035-024-04605-7.

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