Serum and cerebrospinal fluid neurofilament light chain in patients with central nervous system infections caused by varicella-zoster virus

Tobias Tyrberg,Staffan Nilsson,Anna Grahn,Henrik Zetterberg,Kaj Blennow

doi:10.1007/s13365-020-00889-2

Abstract

Varicella-zoster virus (VZV) is a common cause of viral central nervous system (CNS) infection, and patients may suffer from severe neurological sequelae. The biomarker neurofilament light chain (NFL) is used for assessment of neuronal damage and is normally measured in cerebrospinal fluid (CSF). Novel methods have given the possibility to measure NFL in serum instead, which could be a convenient tool to estimate severity of disease and prognosis in VZV CNS infections. Here, we investigate the correlation of serum and CSF NFL in patients with VZV CNS infection and the association of NFL levels in serum and CSF with different VZV CNS entities. NFL in serum and CSF was measured in 61 patients who were retrospectively identified with neurological symptoms and VZV DNA in CSF detected by PCR. Thirty-three herpes zoster patients and 40 healthy blood donors served as control groups. NFL levels in serum and CSF correlated strongly in the patients with VZV CNS infection. Encephalitis was associated with significantly higher levels of NFL in both serum and CSF compared with meningitis and Ramsay Hunt syndrome. Surprisingly, herpes zoster controls had very high serum NFL levels, comparable with those shown in encephalitis patients. We show that analysis of serum NFL can be used instead of CSF NFL for estimation of neuronal injury in patients with VZV CNS infection. However, high levels of serum NFL also in patients with herpes zoster, without signs of CNS involvement, may complicate the interpretation.

Highlights

Varicella-zoster virus (VZV) is a neurotropic virus in the herpes family, and it is one of the most common viral agents causing infection in the central nervous system (CNS) (Granerod et al 2010; Mailles et al 2012; Persson et al 2009)
This study is to our knowledge the first to examine serum neurofilament light chain (NFL) concentrations in patients with VZV CNS infection
Our results indicate that analysis of serum NFL may be used instead of analysis of cerebrospinal fluid (CSF) for estimation of neuronal injury in patients with VZV CNS infection and possibly in other viral CNS infections

Summary

Introduction

Varicella-zoster virus (VZV) is a neurotropic virus in the herpes family, and it is one of the most common viral agents causing infection in the central nervous system (CNS) (Granerod et al 2010; Mailles et al 2012; Persson et al 2009). Reactivation can cause several different clinical manifestations involving the CNS, such as encephalitis, meningitis, myelitis, vasculitis, and cranial nerve affection, including Ramsay Hunt syndrome with peripheral facial palsy (Persson et al 2009). Encephalitis is the most serious manifestation and is associated with both high mortality and morbidity (Mailles et al 2012), but all VZV CNS manifestations may include serious neurological sequels (Persson et al 2009). Different biomarkers measured in cerebrospinal fluid (CSF) or serum may be used for this purpose

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