RT Journal Article
SR Electronic
T1 Comparison of CSF and serum neurofilament light and heavy chain as differential diagnostic biomarkers for ALS
JF Journal of Neurology, Neurosurgery & Psychiatry
JO J Neurol Neurosurg Psychiatry
FD BMJ Publishing Group Ltd
SP 68
OP 74
DO 10.1136/jnnp-2021-327129
VO 93
IS 1
A1 Halbgebauer, Steffen
A1 Steinacker, Petra
A1 Verde, Federico
A1 Weishaupt, Jochen
A1 Oeckl, Patrick
A1 von Arnim, Christine
A1 Dorst, Johannes
A1 Feneberg, Emily
A1 Mayer, Benjamin
A1 Rosenbohm, Angela
A1 Silani, Vincenzo
A1 Ludolph, Albert C
A1 Otto, Markus
YR 2022
UL http://jnnp.bmj.com/content/93/1/68.abstract
AB Objective 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.Methods 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).Results CSF and serum NfL and NfH showed significantly increased levels in ALS (p<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<0.001) than CSF and serum NfH (r=0.68 (95% CI 0.61 to 0.75), p<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).Conclusion 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.All data relevant to the study are included in the article or uploaded as online supplemental information. All data relevant to the study are included in the article and the supplementary information.