Abstract

ObjectiveTo 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.MethodspNfH 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.ResultsThe 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).InterpretationOur 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.

Highlights

  • Amyotrophic lateral sclerosis (ALS) is characterized by progressive degeneration of upper and lower motor neurons.[1]

  • We characterized phosphorylated neurofilament heavy chain (pNfH) levels and their change in serum samples collected before patients were diagnosed with ALS

  • We defined the normal serum pNfH range in a large cohort of healthy controls

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Summary

Introduction

Amyotrophic lateral sclerosis (ALS) is characterized by progressive degeneration of upper and lower motor neurons.[1] To date, there is no cure for ALS. Recent studies demonstrated that the underlying ALS pathophysiology already occurs before the onset of definite symptoms related to ALS. To investigate the presymptomatic phase,[2]. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.

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