Multicenter evaluation of neurofilaments in early symptomatic amyotrophic lateral sclerosis

Feneberg, E; Oeckl, P; Steinacker, P; Verde, F; Barro, C; van Damme, P; Gray, E; Grosskreutz, J; Jardel, C; Kuhle, J; Lamari, F; Mar, D; Mayer, B; Muckova, P; Petri, S; Poesen, K; Raaphorst, J; Salachas, F; Silani, V; Stubendorff, B; Turner, M; Verbeek, M; Weishaupt, J; Ludolph, A; Otto, M

Journal article

Multicenter evaluation of neurofilaments in early symptomatic amyotrophic lateral sclerosis

Abstract:: Objective: To examine Nf concentrations according to symptom onset and clinical diagnostic certainty categories of ALS.

Methods: We measured Nf light chain (NfL) and phosphorylated Nf heavy chain (pNfH) CSF and NfL serum levels in ALS patients with first symptom onset ≤6 months (n=48), >6 months (n=128) from sampling, patients with other neurological diseases, differential diagnoses of a motor neuron disease (MND mimics) and other MND variants to determine the diagnostic accuracy in ALS patients with early symptom onset. Samples were received multicentric and analyzed by ELISA and Simoa platform and related to other clinical parameters.

Results: NfL and pNfH in CSF and NfL in serum were increased in early and later symptomatic phase ALS patients (p<0.0001). CSF and serum NfL and CSF pNfH discriminated ALS patients with early symptom onset from other neurological diseases and MND mimics with high sensitivity (94%, 88%, 98% and 89%, 100%, 78%) and specificity (86%, 92%, 91% and 94%, 90% 98%) and did not vary between clinical diagnostic categories of ALS in the early symptomatic phase group. Baseline NfL and pNfH levels were not significantly different in ALS patients with clinical progression to definite or probable ALS at follow-up.

Conclusions and Relevance: The measurement of Nfs has potential to enhance diagnostic accuracy of ALS in those presenting soon after symptom onset, and is measurable across multiple centers.

Classification of Evidence: This study provides Class II evidence that CSF and serum Nf concentrations discriminate ALS patients with early symptom onset from other neurological diseases.

Publication status:: Published

Peer review status:: Peer reviewed

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APA Style

Feneberg, E., Oeckl, P., Steinacker, P., Verde, F., Barro, C., van Damme, P., Gray, E., Grosskreutz, J., Jardel, C., Kuhle, J., Lamari, F., Mar, D., Mayer, B., Muckova, P., Petri, S., Poesen, K., Raaphorst, J., Salachas, F., Silani, V., … Otto, M. (2017). Multicenter evaluation of neurofilaments in early symptomatic amyotrophic lateral sclerosis. Neurology, 90(1), e22–e30.

MLA Style

Feneberg, E., et al. “Multicenter Evaluation of Neurofilaments in Early Symptomatic Amyotrophic Lateral Sclerosis.” Neurology, vol. 90, no. 1, American Academy of Neurology, 2017, pp. e22–e30.

Chicago Style

Feneberg, E, P Oeckl, P Steinacker, F Verde, C Barro, P van Damme, E Gray, et al. 2017. “Multicenter Evaluation of Neurofilaments in Early Symptomatic Amyotrophic Lateral Sclerosis.” Neurology 90 (1): e22–e30.
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