Tick-Borne Encephalitis: A Differential Pattern of Intrathecal Humoral Immune Response and Inflammatory Cell Composition Compared with Other Viral CNS Infections.

Makbule Senel,Hayrettin Tumani,Jan Lewerenz,Daniel Rapp,Benjamin Mayer,Markus Otto,Sarah Jesse,Sigurd D Süssmuth

doi:10.3390/cells9102169

Makbule Senel, Hayrettin Tumani + Show 6 more

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https://doi.org/10.3390/cells9102169

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Abstract

To investigate whether and how cerebrospinal fluid (CSF) findings can contribute to distinguish tick-borne encephalitis (TBE) from herpes simplex virus (HSV) and varicella zoster virus (VZV) induced central nervous system (CNS) infections (HSV-I, VZV-I). Chart review and identification of TBE, HSV- I, and VZV-I was carried out, fulfilling the following criteria: (1) clinical signs of encephalitis and/or meningitis, (2) complete CSF analysis and confirmed viral etiology by either PCR or antibody testing in CSF, (3) hospitalized patients, and (4) available brain magnetic resonance imaging (MRI). Fifty-nine patients with 118 CSF/serum pairs were included. These comprised 21 with TBE (35 CSF/serum pairs), 20 (40 CSF/serum pairs) with HSV-I, and 18 (43 CSF/serum pairs) with VZV-I. In contrast to HSV-I and VZV-I, CSF cell differentiation in TBE showed more often an increased (>20%) proportion of granulocytes (p < 0.01) and a more frequent quantitative intrathecal IgM synthesis (p = 0.001 and p < 0.01, respectively), while the second was even more pronounced when follow-up CSF analyses were included (p < 0.001). CSF findings help to distinguish TBE from other viral infections. In cases with CSF pleocytosis and a positive history for a stay in or near an endemic area, TBE antibodies in CSF and serum should be determined, especially if granulocytes in CSF cell differentiation and/or an intrathecal IgM synthesis is present.

Highlights

Tick-borne encephalitis (TBE) is an acute inflammatory disease of the central nervous system (CNS) caused by an RNA flavivirus of the same name and transmitted by ticks [1]
A markedly increased proportion of neutrophil granulocytes (>20%) was found significantly more often in tick-borne encephalitis (TBE) (10/21, 48%), compared with 3 (15%) and 1 (6%) patients with herpes simplex virus (HSV)-I and varicella zoster virus (VZV)-I (p < 0.05 and p < 0.01), respectively
Despite an increasing number of TBE cases within the last years, TBE still belongs to the rare diseases

Summary

Introduction

Tick-borne encephalitis (TBE) is an acute inflammatory disease of the central nervous system (CNS) caused by an RNA flavivirus of the same name (tick-borne encephalitis virus, TBEV) and transmitted by ticks [1]. TBEV infection has a biphasic course, with a prodromal phase with flu-like symptoms first, followed by a meningitic/encephalitic phase several days later in some patients. Symptoms range from mild meningitis to severe encephalitis with or without myelitis [2]. TBE is endemic in the Eurasian northern hemisphere, with at least 10,000 cases annually [3], yet it is a rare disease. An increasing incidence of TBE despite the availability of effective vaccines has been described, possibly due to an extended season of the infection and the enlargement of endemic areas [4,5]

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