Objective: To determine whether levels of neurofilament light chain (NFL) in cerebrospinal fluid (CSF) are useful to discriminate between patients with prion disease (PrD) and patients with a diagnosis mimicking Prion disease (PrMim).

Background: NFL is a structural protein of the neural cytoskeleton, essential for axonal growth, transport and signalling. Higher levels of CSF-NFL reflect axonal degeneration. Recently, NFL was shown to also be elevated in Creutzfeld-Jacobs-Disease (CJD) compared to controls and Alzheimer’s disease (AD) patients [1]. To our knowledge no data is available comparing NFL levels of patients with PrD and PrMim. 

Methods: Thirty-one patients with Prion disease as a potential differential diagnosis were evaluated in our hospital between 2010 and 2016. In the diagnostic process CSF was collected using standard procedures. NFL was measured using electrochemiluminiscence immunoessay (NF-light). Total-Tau (t-Tau) was measured using commercially available ELISA kits (Innogenetics NV, Ghent, Belgium).

Results: 10/31 patients fulfilled the diagnosis of Prion disease according to consensus criteria (age 65.5y ± 8.4, male/female=8/2) while 21/31 (66.3y ± 12.3, 8/13) received a different diagnosis after diagnostic workup, including autoimmune encephalopathy, rapidly progressive AD, status epilepticus and frontotemporal dementia. There was no significant difference in CSF levels of NFL between the PrD group (mean 10,654pg/ml, range 3855- 44,9930pg/ml, SD=12,201pg/ml) and the PrMim group (10,781pg/ml, 608-50,000pg/ml, SD=12,347pg/ml), (Kruskal-Wallis, p=0.17). (Figure 1) NFL alone was not useful to discriminate between PrD and PrMim (AUC=0.48), as opposed to CSF t-Tau (PrD: mean 2554 pg/ml, PrMim: mean 1311pg/ml, Kruskal-Wallis, p=0.009, AUC=0.88). A combination of NFL and t-Tau levels did not improve discrimination (AUC= 0.87).

Conclusions: CSF levels of NFL are elevated in patients with PrD. However, there are no significant differences in NFL levels between patients with PrD and PrMim. In contrast to CSF levels of t-Tau, NFL is not useful to discriminate between patients with PrD and patients with PrMim. A combination of NFL and t-Tau did not improve diagnostic accuracy when compared to t-Tau alone. Increased levels of CSF in NFL appear to reflect acuity of neurodegeneration rather than a specific pathophysiological process in PrD.

References: [1] Steinacker P, Blennow K, Halbgebauer S, Shi S, Ruf V, Oeckl P, Giese A, Kuhle J, Slivarichova D, Zetterberg H, Otto M. Neurofilaments in blood and CSF for diagnosis and prediction of onset in Creutzfeldt-Jakob disease. Sci Rep. 2016 Dec 8;6:38737.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/neurofilament-light-chain-levels-in-cerebrospinal-fluid-do-not-discriminate-between-patients-with-prion-disease-and-mimics/