Dysregulation of the Kynurenine Pathway is Related to Persistent Cognitive Impairments After Tick Borne Encephalitis (TBE)

Abstract

Background: Tick-borne encephalitis (TBE) is caused by neurotropic flavivirus infection and is one of the most serious neurological tick-transmitted diseases. TBE patients present long-term post-encephalitic neurologic and neuropsychiatric symptoms including cognitive decline. Importantly, clinical biomarkers and targeted treatments for post-encephalitic symptoms are currently unavailable. It is well known that virus infections induce tryptophan degradation via a cascade of enzymatic steps known as the “kynurenine pathway” (KP). Modulation of kynurenine metabolites during infection represents a finetuned system for regulating immune responses. This KP is also responsible for the biosynthesis of neuroactive compounds such as quinolinic acid (QUIN) and kynurenic acid (KYNA), both capable of impacting cognition. Indeed, altered KP activity has repeatedly been demonstrated in several diseases from which patients suffer cognitive decline. CSF KYNA associates with both poor cognition and psychosis in psychiatric disorders, while concentrations of CSF KYNA and QUIN are found elevated in HIV-1 infected patients and in patients with COVID-19, disorders with a high incidence of long-term cognitive dysfunctions. The present study aims to measure KP metabolites in cerebrospinal fluid (CSF) and serum of TBE patients and to investigate their relation to long-term neurocognitive performance. [...].