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Diagnostic utility of neurofilament markers for MND is limited in restricted disease phenotype and for differentiation from compressive myeloradiculopathies

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Abstract

Misdiagnosis is frequent in early motor neuron disease (MND), typically compressive radiculopathy, or in patients with restricted MND phenotype. In this retrospective, single tertiary centre study, we measured levels of neurofilament light (NfL) and phosphorylated neurofilament heavy (p-NfH) chain in cerebrospinal fluid (CSF) and of p-NfH in serum with commercially available ELISA kits and assessed their respective diagnostic performance as a marker of MND. The entire study population (n = 164) comprised 71 MND patients, 30 patients with compressive myelo- or radiculopathy, and 63 disease controls (DC). Among MND patients, we specified subgroups with only lower motoneuron involvement (MND-LMN, n = 15) and with confounding nerve roots or spinal cord compression (MND-C, n = 18), representing clinical diagnostic pitfalls. MND-LMN displayed significantly lower CSF NfL (p = 0.003) and p-NFH (p = 0.017), but not serum p-NfH (p = 0.347) levels compared to other MND patients (n = 56). The discriminative ability (area under the curve—AUC) of both CSF Nfs towards all MND patients was comparable to each other but significantly higher than that of p-NfH in serum (ps < 0.001). AUC of both CSF Nfs between MND-LMN and DC and also between MND-C and myelo-/radiculopathies were reduced, as compared to AUC between other MND and DC or myelo-/radiculopathies, respectively. Our results suggest that both Nfs in CSF represent a reliable diagnostic marker in a general MND population, fulfilling Awaji criteria. As for diagnostic pitfalls, and also for p-NfH in serum, their discriminative ability and, therefore, clinical utility appears to be limited.

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Data sharing statement

The data used and/or analysed during the current study are available from the corresponding author on reasonable request.

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Funding

This study was supported by the Ministry of Health, Czech Republic—conceptual development of research organization, University Hospital Motol, Prague, Czech Republic grant no. 00064203.

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Authors and Affiliations

  1. Neuromuscular Centre, Department of Neurology, Charles University, 2nd Faculty of Medicine and University Hospital Motol, V Uvalu 84, 150 06, Prague, Czech Republic

    Daniel Baumgartner & Radim Mazanec

  2. Department of Immunology, Charles University, 2nd Faculty of Medicine and University Hospital Motol, V Uvalu 84, 150 06, Prague, Czech Republic

    Jitka Hanzalová

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Contributions

JH performed the experiments; JH and DB contributed to analysis and interpretation of the data. DB and RM recruited the patients, performed the clinical evaluation, and acquired clinical data. DB and RM drafted the manuscript. DB and RM conceptualized and designed the study. All authors had full access to the data in the study, critically revised, and approved the final version of the manuscript. The two (DB, RM) of the three authors of this publication are members of the European Reference Network for Neuromuscular Diseases—Project ID No. 870177.

Corresponding author

Correspondence to Daniel Baumgartner.

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Conflicts of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Patient consent

Informed consent was obtained from the patients who participated in the study.

Ethical approval

The study was approved by the Ethics Committee of the University Hospital Motol, Prague and has, therefore, been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

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Baumgartner, D., Mazanec, R. & Hanzalová, J. Diagnostic utility of neurofilament markers for MND is limited in restricted disease phenotype and for differentiation from compressive myeloradiculopathies. J Neurol 270, 1600–1614 (2023). https://doi.org/10.1007/s00415-022-11504-1

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