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Clinical evaluation of neuroinflammation in child-onset focal epilepsy: a translocator protein PET study

BACKGROUND: Neuroinflammation is associated with various chronic neurological diseases, including epilepsy; however, neuroimaging approaches for visualizing neuroinflammation have not been used in the clinical routine yet. In this study, we used the translocator protein positron emission tomography...

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Autores principales: Kagitani-Shimono, Kuriko, Kato, Hiroki, Kuwayama, Ryoko, Tominaga, Koji, Nabatame, Shin, Kishima, Haruhiko, Hatazawa, Jun, Taniike, Masako
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789379/
https://www.ncbi.nlm.nih.gov/pubmed/33407581
http://dx.doi.org/10.1186/s12974-020-02055-1
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author Kagitani-Shimono, Kuriko
Kato, Hiroki
Kuwayama, Ryoko
Tominaga, Koji
Nabatame, Shin
Kishima, Haruhiko
Hatazawa, Jun
Taniike, Masako
author_facet Kagitani-Shimono, Kuriko
Kato, Hiroki
Kuwayama, Ryoko
Tominaga, Koji
Nabatame, Shin
Kishima, Haruhiko
Hatazawa, Jun
Taniike, Masako
author_sort Kagitani-Shimono, Kuriko
collection PubMed
description BACKGROUND: Neuroinflammation is associated with various chronic neurological diseases, including epilepsy; however, neuroimaging approaches for visualizing neuroinflammation have not been used in the clinical routine yet. In this study, we used the translocator protein positron emission tomography (PET) with [(11)C] DPA713 to investigate neuroinflammation in the epileptogenic zone in patients with child-onset focal epilepsy. METHODS: Patients with intractable focal epilepsy were recruited at the Epilepsy Center of Osaka University; those who were taking any immunosuppressants or steroids were excluded. PET images were acquired for 60 min after intravenous administration of [(11)C] DPA713. The PET image of [(11)C] DPA713 was co-registered to individual’s magnetic resonance imaging (MRI), and the standardized uptake value ratio (SUVr) in regions of interest, which were created in non-lesions and lesions, was calculated using the cerebellum as a pseudo-reference region. In the case of epilepsy surgery, the correlation between SUVr in lesions and pathological findings was analyzed. RESULTS: Twenty-seven patients (mean age: 11.3 ± 6.2 years, male/female: 17/10) were included in this study. Of these, 85.1% showed increased uptake of [(11)C] DPA713 in the focal epileptic lesion. Three patients showed epileptic spasms, suggesting partial seizure onset, and all 18 patients with abnormal lesions on MRI were similarly highlighted by significant uptake of [(11)C] DPA713. DPA713-positive patients had a broad range of etiologies, including focal cortical dysplasia, tumors, infarction, and hippocampal sclerosis. Five out of nine MRI-negative patients showed abnormal [(11)C] DPA713 uptake. The SUVr of [(11)C] DPA713 in lesions was significantly higher than that in non-lesions. In seven patients who underwent epilepsy surgery, increased [(11)C] DPA713 uptake was associated with microglial activation. CONCLUSIONS: This study indicates that [(11)C] DPA713 uptake has valuable sensitivity in the identification of epileptic foci in child-onset focal epilepsy, and inflammation is implicated in the pathophysiology in the epileptic foci caused by various etiologies. Further research is required to establish diagnostic tools for identifying focal epileptogenic zones. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-020-02055-1.
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spelling pubmed-77893792021-01-07 Clinical evaluation of neuroinflammation in child-onset focal epilepsy: a translocator protein PET study Kagitani-Shimono, Kuriko Kato, Hiroki Kuwayama, Ryoko Tominaga, Koji Nabatame, Shin Kishima, Haruhiko Hatazawa, Jun Taniike, Masako J Neuroinflammation Research BACKGROUND: Neuroinflammation is associated with various chronic neurological diseases, including epilepsy; however, neuroimaging approaches for visualizing neuroinflammation have not been used in the clinical routine yet. In this study, we used the translocator protein positron emission tomography (PET) with [(11)C] DPA713 to investigate neuroinflammation in the epileptogenic zone in patients with child-onset focal epilepsy. METHODS: Patients with intractable focal epilepsy were recruited at the Epilepsy Center of Osaka University; those who were taking any immunosuppressants or steroids were excluded. PET images were acquired for 60 min after intravenous administration of [(11)C] DPA713. The PET image of [(11)C] DPA713 was co-registered to individual’s magnetic resonance imaging (MRI), and the standardized uptake value ratio (SUVr) in regions of interest, which were created in non-lesions and lesions, was calculated using the cerebellum as a pseudo-reference region. In the case of epilepsy surgery, the correlation between SUVr in lesions and pathological findings was analyzed. RESULTS: Twenty-seven patients (mean age: 11.3 ± 6.2 years, male/female: 17/10) were included in this study. Of these, 85.1% showed increased uptake of [(11)C] DPA713 in the focal epileptic lesion. Three patients showed epileptic spasms, suggesting partial seizure onset, and all 18 patients with abnormal lesions on MRI were similarly highlighted by significant uptake of [(11)C] DPA713. DPA713-positive patients had a broad range of etiologies, including focal cortical dysplasia, tumors, infarction, and hippocampal sclerosis. Five out of nine MRI-negative patients showed abnormal [(11)C] DPA713 uptake. The SUVr of [(11)C] DPA713 in lesions was significantly higher than that in non-lesions. In seven patients who underwent epilepsy surgery, increased [(11)C] DPA713 uptake was associated with microglial activation. CONCLUSIONS: This study indicates that [(11)C] DPA713 uptake has valuable sensitivity in the identification of epileptic foci in child-onset focal epilepsy, and inflammation is implicated in the pathophysiology in the epileptic foci caused by various etiologies. Further research is required to establish diagnostic tools for identifying focal epileptogenic zones. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-020-02055-1. BioMed Central 2021-01-06 /pmc/articles/PMC7789379/ /pubmed/33407581 http://dx.doi.org/10.1186/s12974-020-02055-1 Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Kagitani-Shimono, Kuriko
Kato, Hiroki
Kuwayama, Ryoko
Tominaga, Koji
Nabatame, Shin
Kishima, Haruhiko
Hatazawa, Jun
Taniike, Masako
Clinical evaluation of neuroinflammation in child-onset focal epilepsy: a translocator protein PET study
title Clinical evaluation of neuroinflammation in child-onset focal epilepsy: a translocator protein PET study
title_full Clinical evaluation of neuroinflammation in child-onset focal epilepsy: a translocator protein PET study
title_fullStr Clinical evaluation of neuroinflammation in child-onset focal epilepsy: a translocator protein PET study
title_full_unstemmed Clinical evaluation of neuroinflammation in child-onset focal epilepsy: a translocator protein PET study
title_short Clinical evaluation of neuroinflammation in child-onset focal epilepsy: a translocator protein PET study
title_sort clinical evaluation of neuroinflammation in child-onset focal epilepsy: a translocator protein pet study
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789379/
https://www.ncbi.nlm.nih.gov/pubmed/33407581
http://dx.doi.org/10.1186/s12974-020-02055-1
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