Westman, G;
Aurelius, E;
Ahlm, C;
Blennow, K;
Eriksson, K;
Lind, L;
Schliamser, S;
... Studahl, M; + view all
(2020)
Cerebrospinal fluid biomarkers of brain injury, inflammation and synaptic autoimmunity predict long-term neurocognitive outcome in herpes simplex encephalitis.
Clinical Microbiology and Infection
10.1016/j.cmi.2020.09.031.
(In press).
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Abstract
OBJECTIVES: To investigate the correlation between biomarkers of brain injury and long-term neurocognitive outcome, and the interplay with intrathecal inflammation and neuronal autoimmunity, in patients with herpes simplex encephalitis (HSE). METHODS: A total of 53 adult/adolescent HSE patients were included from a prospective cohort in a randomized placebo-controlled trial investigating the effect of a 3-month follow-up treatment with valaciclovir. Study subjects underwent repeated serum/CSF sampling and brain MRI the first 3 months along with cognitive assessment by Mattis Dementia Rating Scale (MDRS) during 24 months. CSF samples were analyzed for biomarkers of brain injury, inflammation and synaptic autoimmunity. The pre-defined primary analysis was the correlation between peak CSF neurofilament protein (NFL), a biomarker of neuronal damage, and MDRS at 24 months. RESULTS: Impaired cognitive performance significantly correlated with NFL levels (rho = -0.36, p = 0.020). Development of IgG anti-N-methyl-D-aspartate receptor (NDMAR) antibodies was associated with a broad and prolonged proinflammatory CSF response. In a linear regression model, lower MDRS at 24 months was associated with previous development of IgG anti-NMDAR (beta = -0.6249, p = 0.024) and age (z-score beta = -0.2784, p = 0.024), but not CSF NFL, which however significantly correlated with subsequent NMDAR autoimmunization (p = 0.006). CONCLUSIONS: Our findings show that NFL levels are predictive of long-term neurocognitive outcome in HSE, and suggest a causative chain of events where brain tissue damage increases the risk of NMDAR autoimmunisation and subsequent prolongation of CSF inflammation. The data provides guidance for a future intervention study of immunosuppressive therapy administered in the recovery phase of HSE.
| Type: | Article |
|---|---|
| Title: | Cerebrospinal fluid biomarkers of brain injury, inflammation and synaptic autoimmunity predict long-term neurocognitive outcome in herpes simplex encephalitis |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.cmi.2020.09.031 |
| Publisher version: | https://doi.org/10.1016/j.cmi.2020.09.031 |
| Language: | English |
| Additional information: | © 2020 The Authors. Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Disease under a Creative Commons license (https://creativecommons.org/licenses/by/4.0/). |
| Keywords: | HSV-1, Herpes simplex encephalitis, NFL, NMDAR, antibodies, chemokines, cytokines |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10111377 |
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