Neurofilament light as a marker of neuro‐axonal injury and potential biomarker of disease progression in normal pressure hydrocephalus

Abstract

AbstractBackgroundThe etiology of normal pressure hydrocephalus (NPH) is unknown. Patients worsen but the cause of the progression is unclear. A prognostic biomarker in NPH is required for selecting the best candidates for shunt surgery. Neurofilament‐light chain (NfL) is a marker of neuro‐axonal injury and is elevated in neurodegenerative disease, traumatic brain injury, stroke and encephalitis. The aim of this study was: (1) To compare cerebrospinal fluid (CSF) NfL of NPH patients with healthy controls (HC), and other neurodegenerative diseases: Alzheimer’s disease (AD), and Frontotemporal lobar degeneration (FTLD); and (2) To evaluate CSF NfL levels as a potential biomarker of disease progression in NPH.Method108 patients with CSF analysis: (a) NPH group (39 patients): ventriculomegaly on MRI or CT, negative AD biomarkers, clinical symptoms of NPH, improvement in gait after removal of a large amount of CSF. 14 patients of the unshunted NPH group had a 1‐year follow‐up scan. EVANS index was calculated for these participants; (b) FTLD group (45 patients): 5 behavioural‐variant frontotemporal‐dementia, 19 corticobasal syndrome, 3 frontotemporal dementia with motor neuron disease, 13 progressive supranuclear palsy, 3 semantic‐variant primary progressive aphasia (PPA), and 2 non‐fluent PPA; (c) AD group (19 patients): CSF biomarkers and cognitive symptoms consistent with AD; and (d) HC group (5 participants): cognitively and functionally normal. Levels of NfL in CSF were measured using single molecule array (Simoa) technology. All statistical analyses were corrected for multiple comparisons and age.ResultNfL levels in patients with NPH were significantly higher than HC (1504.7±520 vs 702.5±170pg/ml, p < 0.001), and lower than FTLD group (1504.7±520 vs 3071.7±2830pg/ml, p=0.005). There was a trend for lower NfL in NPH compared to AD, (1504.7±520 vs 2305.4±1179.7pg/ml, p=0.056). There was a significant correlation between baseline NfL levels and increase in EVANS index (r=0.784, p=0.002) in the 14 NPH patients with longitudinal brain imaging.ConclusionCSF NfL levels in NPH patients suggests there is neuro‐axonal injury but is lower than some other neurodegenerative diseases (i.e., FTLD and AD). NfL may be a biomarker for neuro‐axonal injury and disease progression in NPH.