Neurofilament markers for ALS correlate with extent of upper and lower motor neuron disease

Poesen, Koen; De Schaepdryver, Maxim; Stubendorff, Beatrice; Gille, Benjamin; Muckova, Petra; Wendler, Sindy; Prell, Tino; Ringer, Thomas M; Rhode, Heidrun; Stevens, Olivier; Claeys, Kristl G; Couwelier, Goedele; D'Hondt, Ann; Lamaire, Nikita; Tilkin, Petra; Van Reijen, Dimphna; Gourmaud, Sarah; Fedtke, Nadin; Heiling, Bianka; Rumpel, Matthias; Roediger, Annekathrin; Gunkel, Anne; Witte, Otto W; Paquet, Claire; Vandenberghe, Rik; Grosskreutz, Julian; Van Damme, Philip

doi:10.1212/WNL.0000000000004029

Neurofilament markers for ALS correlate with extent of upper and lower motor neuron disease

Author:

Poesen, Koen

De Schaepdryver, Maxim ; Stubendorff, Beatrice ; Gille, Benjamin ; Muckova, Petra ; Wendler, Sindy ; Prell, Tino ; Ringer, Thomas M ; Rhode, Heidrun ; Stevens, Olivier ; Claeys, Kristl G ; Couwelier, Goedele ; D'Hondt, Ann ; Lamaire, Nikita ; Tilkin, Petra ; Van Reijen, Dimphna ; Gourmaud, Sarah ; Fedtke, Nadin ; Heiling, Bianka ; Rumpel, Matthias ; Roediger, Annekathrin ; Gunkel, Anne ; Witte, Otto W ; Paquet, Claire ; Vandenberghe, Rik ; Grosskreutz, Julian ; Van Damme, Philip

Keywords:

Science & Technology, Life Sciences & Biomedicine, Clinical Neurology, Neurosciences & Neurology, AMYOTROPHIC-LATERAL-SCLEROSIS, PROGNOSTIC BIOMARKER, HEAVY-CHAIN, DIAGNOSIS, CSF, PROGRESSION, Adolescent, Adult, Aged, Aged, 80 and over, Amyotrophic Lateral Sclerosis, Biomarkers, Child, Cross-Sectional Studies, Diagnosis, Differential, Disease Progression, Female, Humans, Longitudinal Studies, Male, Middle Aged, Neurofilament Proteins, Phosphorylation, Prognosis, Severity of Illness Index, Single-Blind Method, Young Adult, 1103 Clinical Sciences, 1109 Neurosciences, 1702 Cognitive Sciences, Neurology & Neurosurgery, 3202 Clinical sciences, 3209 Neurosciences

Abstract:

OBJECTIVE: To determine the diagnostic performance and prognostic value of phosphorylated neurofilament heavy chain (pNfH) and neurofilament light chain (NfL) in CSF as possible biomarkers for amyotrophic lateral sclerosis (ALS) at the diagnostic phase. METHODS: We measured CSF pNfH and NfL concentrations in 220 patients with ALS, 316 neurologic disease controls (DC), and 50 genuine disease mimics (DM) to determine and assess the accuracy of the diagnostic cutoff value for pNfH and NfL and to correlate with other clinical parameters. RESULTS: pNfH was most specific for motor neuron disease (specificity 88.2% [confidence interval (CI) 83.0%-92.3%]). pNfH had the best performance to differentially diagnose patients with ALS from DM with a sensitivity of 90.7% (CI 84.9%-94.8%), a specificity of 88.0% (CI 75.7%-95.5%) and a likelihood ratio of 7.6 (CI 3.6-16.0) at a cutoff of 768 pg/mL. CSF pNfH and NfL levels were significantly lower in slow disease progressors, however, with a poor prognostic performance with respect to the disease progression rate. CSF pNfH and NfL levels increased significantly as function of the number of regions with both upper and lower motor involvement. CONCLUSIONS: In particular, CSF pNfH concentrations show an added value as diagnostic biomarkers for ALS, whereas the prognostic value of pNfH and NfL warrants further investigation. Both pNfH and NfL correlated with the extent of motor neuron degeneration. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that elevated concentrations of CSF pNfH and NfL can accurately identify patients with ALS.