Serum and cerebrospinal fluid phosphorylated neurofilament heavy subunit as a marker of neuroaxonal damage in tick-borne encephalitis

Abstract

Extensive axonal and neuronal loss is the main cause of severe manifestations and poor outcomes in tick-borne encephalitis (TBE). Phosphorylated neurofilament heavy subunit (pNF-H) is an essential component of axons, and its detection in cerebrospinal fluid (CSF) or serum can indicate the degree of neuroaxonal damage. We examined the use of pNF-H as a biomarker of neuroaxonal injury in TBE. In 89 patients with acute TBE, we measured CSF levels of pNF-H and 3 other markers of brain injury (glial fibrillary acidic protein, S100B and ubiquitin C-terminal hydrolase L1) and compared the results to those for patients with meningitis of other aetiology and controls. Serum pNF-H levels were measured in 80 patients and compared with findings for 90 healthy blood donors. TBE patients had significantly (P<0.001) higher CSF pNF-H levels than controls as early as hospital admission. Serum pNF-H concentrations were significantly higher in samples from TBE patients collected at hospital discharge (P<0.0001) than in controls. TBE patients with the highest peak values of serum pNF-H, exceeding 10 000 pg ml−1, had a very severe disease course, with coma or tetraplegia. Patients requiring intensive care had significantly higher serum pNF-H levels than other TBE patients (P<0.01). Elevated serum pNF-H values were also observed in patients with incomplete recovery (P<0.05). Peak serum pNF-H levels correlated positively with the duration of hospitalization (P=0.005). Measurement of pNF-H levels in TBE patients might be useful for assessing disease severity and determining prognosis.

Serum and cerebrospinal fluid brain damage markers neurofilament light and glial fibrillary acidic protein correlate with tick‐borne encephalitis disease severity—a multicentre study on Lithuanian and Swedish patients

“…TBE pathogenesis is not fully understood and severe disease in the acute phase has repeatedly been correlated with more sequelae [2, 26]. Interestingly, our findings confirm those from the 2022 Czech study on phosphorylated neurofilament heavy subunit, where a correlation with increased disease severity (duration of hospitalization, admission to the intensive care unit) was found [16]. Neurofilament heavy protein seems to correlate with NfL levels, at least for CSF samples from patients with neurodegenerative diseases [32].…”

“…In TBE patients, few studies have investigated these markers. In a recent report from Czechia, concentrations of phosphorylated neurofilament heavy subunit measured in the CSF were higher in TBE patients than in healthy blood donors [16]. A Polish group found higher CSF concentrations of tau protein and neuron‐specific enolase in TBE patients compared with controls [17, 18].…”

The 2022 Lady Estelle Wolfson lectureship on neurofilaments

“…There are at least five more infectious diseases where elevated Nf concentrations have been associated with neuro-axonal damage and poorer clinical outcome; Herpes encephalitis (HE) (Eckerström et al, 2020;Sellner et al, 2014), Lyme disease, HIV (Alagaratnam, Francesco, et al, 2021;Gisslén et al, 2016;Mellgren et al, 2007), tick-borne encephalitis (Fortova et al, 2022) and…”

“…There are at least five more infectious diseases where elevated Nf concentrations have been associated with neuro‐axonal damage and poorer clinical outcome; Herpes encephalitis (HE) (Eckerström et al, 2020; Li et al, 2019; Sellner et al, 2014), Lyme disease , HIV (Alagaratnam, Francesco, et al, 2021; Gisslén et al, 2016; Mellgren et al, 2007), tick‐borne encephalitis (Fortova et al, 2022) and Progressive multifocal leukoencephalopathy (PML) (Costa et al, 2019; Toorop et al, 2020). Longitudinal Nf concentrations permit also to monitor development of PML in patients that are immunosuppressed (Costa et al, 2019; Loonstra et al, 2019).…”