Weidenfors et al.
Dysregulation of the kynurenine pathway is related to persistent cognition impairment in tick-borne encephalitis. Brain Behav Immun. 2025; In press. doi:10.1016/j.bbi.2025.02.005.
A substantial proportion of TBE patients experience persistent and debilitating residual symptoms following the acute phase of illness, particularly cognitive impairments that can last for months to several years. The underlying mechanisms driving post-encephalitis symptoms remain poorly understood. However, an intriguing connection between infection, inflammation, and cognitive function has been suggested through the immune-mediated degradation of tryptophan (TRP) via the kynurenine pathway (KP), leading to the production of kynurenine (KYN) and its downstream metabolites, including kynurenic acid (KYNA) and quinolinic acid (QUIN).
In a longitudinal study spanning 18 months, researchers investigated the relationship between KP activity and cognitive performance in TBE patients. The findings revealed heightened KP activity in these patients, with increased concentrations of KYN and QUIN, as well as an elevated kynurenine-to-tryptophan ratio (rKT) in both cerebrospinal fluid (CSF) and serum.
Further analyses indicated that serum rKT levels, measured during the acute phase or at the 6-month follow-up, could predict cognitive outcomes. However, absolute KYN concentrations did not show significant associations with cognitive performance metrics such as working memory, attention, and vigilance. Notably, serum QUIN concentrations were inversely correlated with cognitive performance scores at the 6-month follow-up.
In summary, this study provides evidence that dysregulation of the KP in both systemic and intrathecal compartments during acute TBE is associated with the severity of long-term neurocognitive symptoms. Moreover, KP metabolites may serve as potential biomarkers for TBE-related cognitive sequelae.