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Elevated blood purine levels as a biomarker of seizures and epilepsy
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Beamer, Edward, Lacey, Austin, Alves, Mariana, Conte, Giorgia, Tian, Faming, Diego‐Garcia, Laura, Khalil, Mohamed, Rosenow, Felix, Delanty, Norman, Dale, Nicholas, El‐Naggar, Hany, Henshall, David C. and Engel, Tobias (2021) Elevated blood purine levels as a biomarker of seizures and epilepsy. Epilepsia, 62 (3). pp. 817-828. doi:10.1111/epi.16839 ISSN 0013-9580.
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Official URL: http://dx.doi.org/10.1111/epi.16839
Abstract
Objective:
There is a major unmet need for a molecular biomarker of seizures or epilepsy that lends itself to fast, affordable detection in an easy‐to‐use point‐of‐care device. Purines such as adenosine triphosphate and adenosine are potent neuromodulators released during excessive neuronal activity that are also present in biofluids. Their biomarker potential for seizures and epilepsy in peripheral blood has, however, not yet been investigated. The aim of the present study was to determine whether blood purine nucleoside measurements can serve as a biomarker for the recent occurrence of seizures and to support the diagnosis of epilepsy.
Methods:
Blood purine concentrations were measured via a point‐of‐care diagnostic technology based on the summated electrochemical detection of adenosine and adenosine breakdown products (inosine, hypoxanthine, and xanthine; SMARTChip). Measurements of blood purine concentrations were carried out using samples from mice subjected to intra‐amygdala kainic acid‐induced status epilepticus and in video‐electroencephalogram (EEG)‐monitored adult patients with epilepsy.
Results:
In mice, blood purine concentrations were rapidly increased approximately two‐ to threefold after status epilepticus (2.32 ± .40 µmol·L–1 [control] vs. 8.93 ± 1.03 µmol·L–1 [after status epilepticus]), and levels correlated with seizure burden and postseizure neurodegeneration in the hippocampus. Blood purine concentrations were also elevated in patients with video‐EEG‐diagnosed epilepsy (2.39 ± .34 µmol·L–1 [control, n = 13] vs. 4.35 ± .38 µmol·L–1 [epilepsy, n = 26]).
Significance:
Our data provide proof of concept that the measurement of blood purine concentrations may offer a rapid, low‐volume bedside test to support the diagnosis of seizures and epilepsy.
Item Type: | Journal Article | |||||||||||||||||||||||||||
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Subjects: | R Medicine > RC Internal medicine | |||||||||||||||||||||||||||
Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | |||||||||||||||||||||||||||
Library of Congress Subject Headings (LCSH): | Epilepsy, Purines, Spasms, Biochemical markers -- Diagnostic use | |||||||||||||||||||||||||||
Journal or Publication Title: | Epilepsia | |||||||||||||||||||||||||||
Publisher: | Wiley-Blackwell Publishing Ltd. | |||||||||||||||||||||||||||
ISSN: | 0013-9580 | |||||||||||||||||||||||||||
Official Date: | 5 March 2021 | |||||||||||||||||||||||||||
Dates: |
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Volume: | 62 | |||||||||||||||||||||||||||
Number: | 3 | |||||||||||||||||||||||||||
Page Range: | pp. 817-828 | |||||||||||||||||||||||||||
DOI: | 10.1111/epi.16839 | |||||||||||||||||||||||||||
Status: | Peer Reviewed | |||||||||||||||||||||||||||
Publication Status: | Published | |||||||||||||||||||||||||||
Reuse Statement (publisher, data, author rights): | This is the peer reviewed version of the following article: Beamer, E., Lacey, A., Alves, M., Conte, G., Tian, F., de Diego‐Garcia, L., Khalil, M., Rosenow, F., Delanty, N., Dale, N., El‐Naggar, H., Henshall, D.C. and Engel, T. (2021), Elevated blood purine levels as a biomarker of seizures and epilepsy. Epilepsia, 62: 817-828. https://doi.org/10.1111/epi.16839, which has been published in final form at https://doi.org/10.1111/epi.16839. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. | |||||||||||||||||||||||||||
Access rights to Published version: | Restricted or Subscription Access | |||||||||||||||||||||||||||
Date of first compliant deposit: | 12 March 2021 | |||||||||||||||||||||||||||
Date of first compliant Open Access: | 18 February 2022 | |||||||||||||||||||||||||||
RIOXX Funder/Project Grant: |
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