CSF neurofilament protein analysis in the differential diagnosis of ALS

Cerebrospinal fluid (CSF) biomarkers have been studied to differentiate between patients with ALS and neurological controls, but not in comparison to clinically more relevant disorders mimicking ALS.

In this retrospective study, CSF concentrations of various brain-specific proteins were analyzed in patients with ALS (n = 32) and ALS-mimic disorders (n = 26).

CSF concentrations of neurofilament light (NFL) and heavy chain (NFHp35), but not other brain-specific proteins, were significantly higher in patients with ALS than in patients with an ALS-mimic disorder, however with maximum sensitivity or specificity of 80%. The mean CSF level of NFHp35 was 781 ng/L in the ALS group vs. 338 ng/L in the ALS-mimic disorders group and for NFL the mean CSF levels were 62 ng/L vs. 24 ng/L.

Although CSF concentrations of NFL and NFHp35 are higher in patients with ALS, the diagnostic accuracy for differentiating ALS from ALS-mimic disorders seems insufficient. Our results suggest that, in the clinical work-up of patients suspected of ALS, application of CSF analysis alone is limited but may have potential in combination with other clinical and electrophysiological markers.