title: Sustained elevation of kynurenic Acid in the cerebrospinal fluid of patients with herpes simplex virus type 1 encephalitis.
abstract: Herpes simplex virus (HSV) type 1 encephalitis (HSE) is a viral infectious disease with commonly occurring neurodegeneration and neurological/cognitive long-term sequelae. Kynurenic acid (KYNA) is a neuroactive tryptophan metabolite, which is elevated in the cerebrospinal fluid (CSF) during viral infection as a result of immune activation. The aim of the study was to investigate the role of endogenous brain KYNA for the long-term outcome of the disease. CSF KYNA concentration was analyzed in 25 HSE patients along the course of the disease and compared with that of 25 age-matched healthy volunteers. Within 3 weeks of admission CSF KYNA of HSE patients was markedly elevated (median 33.6 nM) compared to healthy volunteers (median 1.45 nM). Following a decline observed after 1-2 months, levels of CSF KYNA were elevated more than 1 year after admission (median 3.4 nM range: 1-9 years). A negative correlation was found between initial CSF KYNA concentrations and severity of the long-term sequelae. This study show a marked elevation in CSF KYNA from patients with HSE, most pronounced during the acute phase of the disease and slowly declining along the recovery. We propose that brain KYNA might potentially protect against neurodegeneration while causing a long-lasting loss in cognitive function associated with the disease.
authors: Infectious Diseases Unit, Department of Medicine, Karolinska University Hospital, Stockholm, Sweden.
authors: Ann
authors: A
authors: Atlas
authors: Elisabeth
authors: E
authors: Franzen-Röhl
authors: Johan
authors: J
authors: Söderlund
authors: Erik G
authors: EG
authors: Jönsson
authors: Martin
authors: M
authors: Samuelsson
authors: Lilly
authors: L
authors: Schwieler
authors: Birgit
authors: B
authors: Sköldenberg
authors: Göran
authors: G
authors: Engberg
keywords: HSE; NMDA hypofunction; Tryptophan; cognition; neurodegeneration