• Petra Steinacker, Emily Feneberg, Jochen Weishaupt, Johannes Brettschneider, Hayrettin Tumani, Peter M Andersen, Christine A F von Arnim, Sarah Böhm, Jan Kassubek, Christian Kubisch, Dorothée Lulé, Hans-Peter Müller, Rainer Muche, Elmar Pinkhardt, Patrick Oeckl, Angela Rosenbohm, Sarah Anderl-Straub, Alexander E Volk, Patrick Weydt, Albert C Ludolph, and Markus Otto.
• Department of Neurology, University of Ulm, Ulm, Germany.
• J. Neurol. Neurosurg. Psychiatr. 2016 Jan 1; 87 (1): 12-20.

ObjectivesBiomarkers for the diagnosis of motoneuron diseases (MND) are urgently needed to improve the diagnostic pathway, patient stratification and monitoring. The aim of this study was to validate candidate markers for MND in cerebrospinal fluid (CSF) and specify cut-offs based on large patient cohorts by especially considering patients who were seen under the initial differential diagnosis (MND mimics).MethodsIn a prospective study, we investigated CSF of 455 patients for neurofilament light chain (NfL), phosphorylated heavy chain (pNfH), tau protein (Tau) and phospho-tau protein (pTau). Analysed cohorts included patients with apparently sporadic and familial amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS) (MND, n=253), MND mimics (n=85) and neurological control groups. Cut-off values were specified, and diagnostic performance and correlation with progression were analysed.ResultsNfs were significantly higher in the MND group compared to the control groups, whereas Tau and pTau did not differ. At a cut-off level of 2200 pg/mL for NfL, a 77% diagnostic sensitivity (CI 71% to 82%), 85% specificity (CI 79% to 90%) and 87% positive predictive value (PPV) (CI 81% to 91%) were achieved. For pNfH, we calculated 83% sensitivity (CI 78% to 88%), 77% specificity (CI 71% to 83%) and 82% PPV (CI 77% to 86%) at 560 pg/mL. There were no significant differences between sporadic and genetic ALS or PLS. Nf levels were elevated at early disease stage, and correlated moderately with MND progression and duration.ConclusionsNeurofilaments in CSF have a high relevance for the differential diagnosis of MNDs and should be included in the diagnostic work-up of patients. Their value as prognostic markers should be investigated further.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

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