Neurofilament light chain marks severity of papilledema in idiopathic intracranial hypertension

Abstract

Background: Neurofilament light chain (NfL) reflects axonal damage in neurological disorders. It has recently been evaluated in idiopathic intracranial hypertension (IIH). A biomarker indicating the severity of optic nerve damage in IIH could support diagnostic accuracy and therapeutic decisions.

Methods: We retrospectively reviewed NfL concentrations in the cerebrospinal fluid (CSF) of 35 IIH patients and 12 healthy controls, who had received diagnostic workup for IIH in our clinic. The diagnosis of IIH was made according to the modified Friedman criteria for IIH and for IIH without papilledema Friedman DI et al Neurol 81:1159-1165 (2013) [1]. NfL in the CSF (CSF-NfL) was correlated with the severity of papilledema and with CSF opening pressure.

Results: CSF-NfL correlated with CSF opening pressure at the time of collection. In patients with IIH and moderate or severe papilledema, CSF-NfL was significantly increased compared to patients with mild or no papilledema. Healthy controls with raised intracranial pressure showed no relevant elevation of CSF-NfL.

Conclusion: CSF-NfL appears to correlate with the severity of papilledema in IIH and with CSF opening pressure and may therefore be a predictor of optic nerve damage in IIH patients.

Keywords: CSF opening pressure; Idiopathic intracranial hypertension; Neurofilament light chain; Papilledema.

Fig. 1

Flow-chart of patient selection. Out of 59 patients admitted to our hospital for suspected IIH, 6 were excluded because of incomplete diagnostic workup. Six were excluded because different neurological disorders were found. Among the 47 remaining patients, 35 met the Friedman diagnostic criteria for IIH/IIHWOP. The existence of IIH and other neurological disorders was ruled out in 12 patients, which were used as healthy controls

Fig. 2

Correlation of CSF-NfL and CSF opening pressure of all patients (IIH/IIHWOP and healthy controls, Pearson correlation). The correlation coefficient of r = 0.50 indicates a moderate correlation of CSF-NfL ratios with CSF opening pressure. The vertical bar indicates the 25 cmH₂O cut off for pathologically elevated CSF pressure

Fig. 3

Grouped dot plot comparing the individual CSF-NfL ratio (CSF-NfL/age-adjusted normal value) in all subjects depending on the grade of papilledema. Each dot indicates the CSF-NfL ratio per individual patient. Dashes indicate mean values for each group

Fig. 4

Two box-whisker plots comparing CSF-NfL ratios between the two subgroups of patients with no or with mild papilledema (group 1, n = 24; 7) and in patients with moderate or severe papilledema (group 2, n = 9; 7). The first group (none and mild papilledema) had a mean CSF-NfL ratio of 0.8 ± 0.4. The group with moderate and severe papilledema showed a higher mean CSF-NfL ratio of 2.1 ± 1.3. Unpaired t-test showed a significant difference regarding CSF-NfL ratios between the two groups (i.e., p < 0.0001)