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Metabolic patterns in brain (18)F-fluorodeoxyglucose PET relate to aetiology in paediatric dystonia

There is a lack of imaging markers revealing the functional characteristics of different brain regions in paediatric dystonia. In this observational study, we assessed the utility of [(18)F]2-fluoro-2-deoxy-D-glucose (FDG)-PET in understanding dystonia pathophysiology by revealing specific resting a...

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Autores principales: Tsagkaris, Stavros, Yau, Eric K C, McClelland, Verity, Papandreou, Apostolos, Siddiqui, Ata, Lumsden, Daniel E, Kaminska, Margaret, Guedj, Eric, Hammers, Alexander, Lin, Jean-Pierre
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10232264/
https://www.ncbi.nlm.nih.gov/pubmed/36445406
http://dx.doi.org/10.1093/brain/awac439
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author Tsagkaris, Stavros
Yau, Eric K C
McClelland, Verity
Papandreou, Apostolos
Siddiqui, Ata
Lumsden, Daniel E
Kaminska, Margaret
Guedj, Eric
Hammers, Alexander
Lin, Jean-Pierre
author_facet Tsagkaris, Stavros
Yau, Eric K C
McClelland, Verity
Papandreou, Apostolos
Siddiqui, Ata
Lumsden, Daniel E
Kaminska, Margaret
Guedj, Eric
Hammers, Alexander
Lin, Jean-Pierre
author_sort Tsagkaris, Stavros
collection PubMed
description There is a lack of imaging markers revealing the functional characteristics of different brain regions in paediatric dystonia. In this observational study, we assessed the utility of [(18)F]2-fluoro-2-deoxy-D-glucose (FDG)-PET in understanding dystonia pathophysiology by revealing specific resting awake brain glucose metabolism patterns in different childhood dystonia subgroups. PET scans from 267 children with dystonia being evaluated for possible deep brain stimulation surgery between September 2007 and February 2018 at Evelina London Children’s Hospital (ELCH), UK, were examined. Scans without gross anatomical abnormality (e.g. large cysts, significant ventriculomegaly; n = 240) were analysed with Statistical Parametric Mapping (SPM12). Glucose metabolism patterns were examined in the 144/240 (60%) cases with the 10 commonest childhood-onset dystonias, focusing on nine anatomical regions. A group of 39 adult controls was used for comparisons. The genetic dystonias were associated with the following genes: TOR1A, THAP1, SGCE, KMT2B, HPRT1 (Lesch Nyhan disease), PANK2 and GCDH (Glutaric Aciduria type 1). The acquired cerebral palsy (CP) cases were divided into those related to prematurity (CP-Preterm), neonatal jaundice/kernicterus (CP-Kernicterus) and hypoxic-ischaemic encephalopathy (CP-Term). Each dystonia subgroup had distinct patterns of altered FDG-PET uptake. Focal glucose hypometabolism of the pallidi, putamina or both, was the commonest finding, except in PANK2, where basal ganglia metabolism appeared normal. HPRT1 uniquely showed glucose hypometabolism across all nine cerebral regions. Temporal lobe glucose hypometabolism was found in KMT2B, HPRT1 and CP-Kernicterus. Frontal lobe hypometabolism was found in SGCE, HPRT1 and PANK2. Thalamic and brainstem hypometabolism were seen only in HPRT1, CP-Preterm and CP-term dystonia cases. The combination of frontal and parietal lobe hypermetabolism was uniquely found in CP-term cases. PANK2 cases showed a distinct combination of parietal hypermetabolism with cerebellar hypometabolism but intact putaminal-pallidal glucose metabolism. HPRT1, PANK2, CP-kernicterus and CP-preterm cases had cerebellar and insula glucose hypometabolism as well as parietal glucose hypermetabolism. The study findings offer insights into the pathophysiology of dystonia and support the network theory for dystonia pathogenesis. ‘Signature’ patterns for each dystonia subgroup could be a useful biomarker to guide differential diagnosis and inform personalized management strategies.
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spelling pubmed-102322642023-06-01 Metabolic patterns in brain (18)F-fluorodeoxyglucose PET relate to aetiology in paediatric dystonia Tsagkaris, Stavros Yau, Eric K C McClelland, Verity Papandreou, Apostolos Siddiqui, Ata Lumsden, Daniel E Kaminska, Margaret Guedj, Eric Hammers, Alexander Lin, Jean-Pierre Brain Original Article There is a lack of imaging markers revealing the functional characteristics of different brain regions in paediatric dystonia. In this observational study, we assessed the utility of [(18)F]2-fluoro-2-deoxy-D-glucose (FDG)-PET in understanding dystonia pathophysiology by revealing specific resting awake brain glucose metabolism patterns in different childhood dystonia subgroups. PET scans from 267 children with dystonia being evaluated for possible deep brain stimulation surgery between September 2007 and February 2018 at Evelina London Children’s Hospital (ELCH), UK, were examined. Scans without gross anatomical abnormality (e.g. large cysts, significant ventriculomegaly; n = 240) were analysed with Statistical Parametric Mapping (SPM12). Glucose metabolism patterns were examined in the 144/240 (60%) cases with the 10 commonest childhood-onset dystonias, focusing on nine anatomical regions. A group of 39 adult controls was used for comparisons. The genetic dystonias were associated with the following genes: TOR1A, THAP1, SGCE, KMT2B, HPRT1 (Lesch Nyhan disease), PANK2 and GCDH (Glutaric Aciduria type 1). The acquired cerebral palsy (CP) cases were divided into those related to prematurity (CP-Preterm), neonatal jaundice/kernicterus (CP-Kernicterus) and hypoxic-ischaemic encephalopathy (CP-Term). Each dystonia subgroup had distinct patterns of altered FDG-PET uptake. Focal glucose hypometabolism of the pallidi, putamina or both, was the commonest finding, except in PANK2, where basal ganglia metabolism appeared normal. HPRT1 uniquely showed glucose hypometabolism across all nine cerebral regions. Temporal lobe glucose hypometabolism was found in KMT2B, HPRT1 and CP-Kernicterus. Frontal lobe hypometabolism was found in SGCE, HPRT1 and PANK2. Thalamic and brainstem hypometabolism were seen only in HPRT1, CP-Preterm and CP-term dystonia cases. The combination of frontal and parietal lobe hypermetabolism was uniquely found in CP-term cases. PANK2 cases showed a distinct combination of parietal hypermetabolism with cerebellar hypometabolism but intact putaminal-pallidal glucose metabolism. HPRT1, PANK2, CP-kernicterus and CP-preterm cases had cerebellar and insula glucose hypometabolism as well as parietal glucose hypermetabolism. The study findings offer insights into the pathophysiology of dystonia and support the network theory for dystonia pathogenesis. ‘Signature’ patterns for each dystonia subgroup could be a useful biomarker to guide differential diagnosis and inform personalized management strategies. Oxford University Press 2022-11-29 /pmc/articles/PMC10232264/ /pubmed/36445406 http://dx.doi.org/10.1093/brain/awac439 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Tsagkaris, Stavros
Yau, Eric K C
McClelland, Verity
Papandreou, Apostolos
Siddiqui, Ata
Lumsden, Daniel E
Kaminska, Margaret
Guedj, Eric
Hammers, Alexander
Lin, Jean-Pierre
Metabolic patterns in brain (18)F-fluorodeoxyglucose PET relate to aetiology in paediatric dystonia
title Metabolic patterns in brain (18)F-fluorodeoxyglucose PET relate to aetiology in paediatric dystonia
title_full Metabolic patterns in brain (18)F-fluorodeoxyglucose PET relate to aetiology in paediatric dystonia
title_fullStr Metabolic patterns in brain (18)F-fluorodeoxyglucose PET relate to aetiology in paediatric dystonia
title_full_unstemmed Metabolic patterns in brain (18)F-fluorodeoxyglucose PET relate to aetiology in paediatric dystonia
title_short Metabolic patterns in brain (18)F-fluorodeoxyglucose PET relate to aetiology in paediatric dystonia
title_sort metabolic patterns in brain (18)f-fluorodeoxyglucose pet relate to aetiology in paediatric dystonia
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10232264/
https://www.ncbi.nlm.nih.gov/pubmed/36445406
http://dx.doi.org/10.1093/brain/awac439
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