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Halbgebauer, Steffen; Steinacker, Petra; Verde, Federico; Weishaupt, Jochen; Oeckl, Patrick; von Arnim, Christine; Dorst, Johannes; Feneberg, Emily; Mayer, Benjamin; Rosenbohm, Angela; Silani, Vincenzo; Ludolph, Albert C; Otto, Markus

Comparison of CSF and serum neurofilament light and heavy chain as differential diagnostic biomarkers for ALS

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  • Medientyp: E-Artikel
  • Titel: Comparison of CSF and serum neurofilament light and heavy chain as differential diagnostic biomarkers for ALS
  • Beteiligte: Halbgebauer, Steffen; Steinacker, Petra; Verde, Federico; Weishaupt, Jochen; Oeckl, Patrick; von Arnim, Christine; Dorst, Johannes; Feneberg, Emily; Mayer, Benjamin; Rosenbohm, Angela; Silani, Vincenzo; Ludolph, Albert C; Otto, Markus
  • Erschienen: BMJ, 2022
  • Erschienen in: Journal of Neurology, Neurosurgery & Psychiatry
  • Sprache: Englisch
  • DOI: 10.1136/jnnp-2021-327129
  • ISSN: 1468-330X; 0022-3050
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:sec><jats:title>Objective</jats:title><jats:p>Elevated levels of neurofilament light (NfL) and heavy (NfH) chain in amyotrophic lateral sclerosis (ALS) cerebrospinal fluid (CSF) and serum reflect neuro-axonal degeneration and are used as diagnostic biomarkers. However, studies comparing the differential diagnostic potential for ALS of all four parameters are missing. Here, we measured serum NfL/NfH and CSF NfL/NfH in a large cohort of ALS and other neurological disorders and analysed the differential diagnostic potential.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>In total CSF and serum of 294 patients were analysed. The diagnostic groups comprised: ALS (n=75), frontotemporal lobar degeneration (FTLD) (n=33), Alzheimer’s disease (n=20), Parkinson’s disease (dementia) (n=18), Creutzfeldt-Jakob disease (n=11), non-neurodegenerative controls (n=77) (Con) and 60 patients who were seen under the direct differential diagnosis of a patient with ALS (Con.DD).</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>CSF and serum NfL and NfH showed significantly increased levels in ALS (p&lt;0.0001) compared with Con and Con.DD. The difference between ALS and FTLD was markedly stronger for NfH than for NfL. CSF and serum NfL demonstrated a stronger correlation (r=0.84 (95% CI 0.80 to 0.87), p&lt;0.001) than CSF and serum NfH (r=0.68 (95% CI 0.61 to 0.75), p&lt;0.0001). Comparing ALS and Con.DD, receiver operating characteristic analysis revealed the best area under the curve (AUC) value for CSF NfL (AUC=0.94, 95% CI 0.91 to 0.98), followed by CSF NfH (0.93, 95% CI 0.88 to 0.98), serum NfL (0.93, 95% CI 0.89 to 0.97) and serum NfH (0.88, 95% CI 0.82 to 0.94).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Our results demonstrate that CSF NfL and NfH as well as serum NfL are equally suited for the differential diagnosis of ALS, whereas serum NfH appears to be slightly less potent.</jats:p></jats:sec>