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Remodeling of the neuromuscular junction in myasthenia gravis increases serum neurofilament heavy chain levels

Wong, Sui H; Petzold, Axel; (2023) Remodeling of the neuromuscular junction in myasthenia gravis increases serum neurofilament heavy chain levels. Muscle Nerve , 68 (1) pp. 91-94. 10.1002/mus.27838. Green open access

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Abstract

INTRODUCTION/AIMS: In myasthenia gravis, prolonged muscle denervation causes muscle atrophy. We re-visited this observation using a biomarker hypothesis. We tested if serum neurofilament heavy chain levels, a biomarker for axonal degeneration, were elevated in myasthenia gravis. METHODS: We enrolled 70 patients with isolated ocular myasthenia gravis and 74 controls recruited from patients in the emergency department. Demographic data were collected alongside serum samples. Serum samples were analyzed by enzyme-linked immunosorbent assay (ELISA) for the neurofilament heavy chain (NfH-SMI35). The statistical analyses included group comparisons, receiver operator characteristic (ROC) curves, area under the curve (AUC), sensitivity, specificity, and positive and negative predictive values. RESULTS: Serum neurofilament heavy chain levels were significantly (p < 0.0001) higher in individuals with myasthenia gravis (0.19 ng/mL) than in healthy control subjects (0.07 ng/mL). A ROC AUC optimized cutoff level of 0.06 ng/mL gave a diagnostic sensitivity of 82%, specificity of 76%, positive predictive value of 0.77 and a negative predictive value of 0.81. DISCUSSION: The increase of serum neurofilament heavy chain levels in myasthenia gravis is consistent with observations of muscle denervation. We suggest that there is ongoing remodeling of the neuromuscular junction in myasthenia gravis. Longitudinal quantification of neurofilament isoform levels will be needed to investigate the prognostic value and potentially guide treatment decisions.

Type: Article
Title: Remodeling of the neuromuscular junction in myasthenia gravis increases serum neurofilament heavy chain levels
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/mus.27838
Publisher version: https://doi.org/10.1002/mus.27838
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.
Keywords: biomarker, myasthenia gravis, neuro-muscular junction, neurofilament, ocular myasthenia gravis
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
URI: https://discovery.ucl.ac.uk/id/eprint/10169464
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