Cerebrospinal fluid biomarkers of brain injury, inflammation and synaptic autoimmunity predict long-term neurocognitive outcome in herpes simplex encephalitis
(2021) In Clinical Microbiology and Infection 27(8). p.1131-1136- Abstract
Objectives: The aim was 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/cerebrospinal fluid (CSF) sampling and brain magnetic resonance imaging in the first 3 months along with cognitive assessment using the Mattis Dementia Rating Scale (MDRS) at 24 months. CSF samples were analysed for biomarkers of brain... (More)
Objectives: The aim was 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/cerebrospinal fluid (CSF) sampling and brain magnetic resonance imaging in the first 3 months along with cognitive assessment using the Mattis Dementia Rating Scale (MDRS) at 24 months. CSF samples were analysed for biomarkers of brain injury, inflammation and synaptic autoimmunity. The predefined 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-N-methyl-D-aspartate receptor (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). Discussion: 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.
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- author
- Westman, Gabriel ; Aurelius, Elisabeth ; Ahlm, Clas ; Blennow, Kaj LU ; Eriksson, Kristina ; Lind, Liza ; Schliamser, Silvia LU ; Sund, Fredrik ; Zetterberg, Henrik LU and Studahl, Marie
- organization
- publishing date
- 2021-08-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Antibodies chemokines, Cytokines, Herpes simplex encephalitis, HSV-1, NFL, NMDAR
- in
- Clinical Microbiology and Infection
- volume
- 27
- issue
- 8
- pages
- 6 pages
- publisher
- Wiley-Blackwell
- external identifiers
-
- scopus:85094938923
- pmid:32979577
- ISSN
- 1198-743X
- DOI
- 10.1016/j.cmi.2020.09.031
- language
- English
- LU publication?
- yes
- id
- 552a179b-d9e6-44d3-b443-5348025dc55f
- date added to LUP
- 2020-11-23 13:37:49
- date last changed
- 2024-06-13 00:28:30
@article{552a179b-d9e6-44d3-b443-5348025dc55f,
abstract = {{<p>Objectives: The aim was 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/cerebrospinal fluid (CSF) sampling and brain magnetic resonance imaging in the first 3 months along with cognitive assessment using the Mattis Dementia Rating Scale (MDRS) at 24 months. CSF samples were analysed for biomarkers of brain injury, inflammation and synaptic autoimmunity. The predefined 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-N-methyl-D-aspartate receptor (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). Discussion: 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.</p>}},
author = {{Westman, Gabriel and Aurelius, Elisabeth and Ahlm, Clas and Blennow, Kaj and Eriksson, Kristina and Lind, Liza and Schliamser, Silvia and Sund, Fredrik and Zetterberg, Henrik and Studahl, Marie}},
issn = {{1198-743X}},
keywords = {{Antibodies chemokines; Cytokines; Herpes simplex encephalitis; HSV-1; NFL; NMDAR}},
language = {{eng}},
month = {{08}},
number = {{8}},
pages = {{1131--1136}},
publisher = {{Wiley-Blackwell}},
series = {{Clinical Microbiology and Infection}},
title = {{Cerebrospinal fluid biomarkers of brain injury, inflammation and synaptic autoimmunity predict long-term neurocognitive outcome in herpes simplex encephalitis}},
url = {{http://dx.doi.org/10.1016/j.cmi.2020.09.031}},
doi = {{10.1016/j.cmi.2020.09.031}},
volume = {{27}},
year = {{2021}},
}