Multicenter evaluation of neurofilaments in early symptom onset amyotrophic lateral sclerosis
Top Cited Papers
- 2 January 2018
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Neurology
- Vol. 90 (1), e22-e30
- https://doi.org/10.1212/wnl.0000000000004761
Abstract
Objective To examine neurofilament (Nf) concentrations according to symptom onset and clinical diagnostic certainty categories of amyotrophic lateral sclerosis (ALS). Methods We measured Nf light chain (NfL) and phosphorylated Nf heavy chain (pNfH) CSF and NfL serum levels in patients with ALS with first symptom onset ≤6 months (n = 54) or >6 months (n = 135) from sampling, and patients with other neurologic diseases, differential diagnoses of a motor neuron disease (MND mimics), and other MND variants to determine the diagnostic accuracy in patients with ALS with early symptom onset. Samples were received multicentric and analyzed by ELISA and Simoa platform and related to other clinical measures. Results NfL and pNfH in CSF and NfL in serum were increased in early and later symptomatic phase ALS (p < 0.0001). CSF and serum NfL and CSF pNfH discriminated patients with ALS with early symptom onset from those with other neurologic 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 patients with ALS with clinical progression to definite or probable ALS at follow-up. Conclusion The measurement of Nf 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 with early symptom onset from other neurologic diseases.Keywords
This publication has 30 references indexed in Scilit:
- Amyotrophic lateral sclerosis: moving towards a new classification systemThe Lancet Neurology, 2016
- CSF neurofilament light chain reflects corticospinal tract degeneration in ALSAnnals of Clinical and Translational Neurology, 2015
- Ensuring continued progress in biomarkers for amyotrophic lateral sclerosisMuscle & Nerve, 2014
- Roadmap and standard operating procedures for biobanking and discovery of neurochemical markers in ALSAmyotrophic Lateral Sclerosis, 2012
- Amyotrophic lateral sclerosisThe Lancet, 2011
- CSF neurofilament protein analysis in the differential diagnosis of ALSZeitschrift für Neurologie, 2009
- Axonal damage markers in cerebrospinal fluid are increased in ALSNeurology, 2006
- El Escorial revisited: Revised criteria for the diagnosis of amyotrophic lateral sclerosisAmyotrophic Lateral Sclerosis, 2000
- Patients with Amyotrophic Lateral Sclerosis and Other Neurodegenerative Diseases Have Increased Levels of Neurofilament Protein in CSFJournal of Neurochemistry, 1996
- El escorial World Federation of Neurology criteria for the diagnosis of amyotrophic lateral sclerosisJournal of the Neurological Sciences, 1994