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Serum neurofilament heavy chains as early marker of motor neuron degeneration
Author(s) -
De Schaepdryver Maxim,
Goossens Janne,
De Meyer Steffi,
Jeromin Andreas,
Masrori Pegah,
Brix Britta,
Claeys Kristl G.,
Schaeverbeke Jolien,
Adamczuk Katarzyna,
Vandenberghe Rik,
Van Damme Philip,
Poesen Koen
Publication year - 2019
Publication title -
annals of clinical and translational neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.824
H-Index - 42
ISSN - 2328-9503
DOI - 10.1002/acn3.50890
Subject(s) - medicine , hazard ratio , amyotrophic lateral sclerosis , percentile , gastroenterology , confidence interval , univariate analysis , multivariate analysis , disease , statistics , mathematics
Objective To determine whether serum phosphorylated neurofilament heavy chain (pNfH) levels are elevated before patients were diagnosed with sporadic or familial ALS, and what the prognostic value of these prediagnostic pNfH levels is. Methods pNfH was measured via ELISA in leftovers of serum drawn for routine purposes before the time of diagnosis. These prediagnostic samples were retrieved from the biobank of the University Hospitals Leuven for 95 patients who in follow‐up received a diagnosis of ALS. Additionally, 35 patients with mild cognitive impairment (MCI) and 85 healthy controls (HC) were included in this retrospective study. Results The median disease duration (range) from onset to prediagnostic sampling and from onset to diagnosis was 6.5 (−71.9–36.1) and 9.9 (2.0–40.7) months, respectively. Fifty‐eight percent of the prediagnostic samples had serum pNfH levels above the 95th percentile of pNfH levels measured in HC. Serum pNfH levels (median (range)) were elevated up to 18 months before the diagnosis of ALS (91 pg/mL (6–342 pg/mL)) in comparison with HC (30 pg/mL (6–146 pg/mL); P  = 0.05), and increased during the prediagnostic stage, which was not observed in patients with MCI. Furthermore, prediagnostic pNfH levels were a univariate predictor of survival in ALS (hazard ratio (95% CI): 2.16 (1.20–3.87); P  = 0.01). Interpretation Our findings demonstrate that serum pNfH is elevated well before the time of diagnosis in mainly sporadic ALS patients. These results encourage to prospectively explore if pNfH has an added value to shorten the diagnostic delay in ALS.

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