Hypometabolism and atrophy patterns associated with Niemann-Pick type C

Background Niemann-Pick disease type C (NP-C) is a rare genetic lysosomal lipid storage disorder characterized by progressive neurological impairment. Early diagnosis is critical for initiating treatment with miglustat, which can decelerate disease progression. In this study, we evaluated a cohort o...

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Autores: Silva-Rodríguez, Jesús, Castro, Cristina, Cortés, Julia, Arias, Manuel, Pubul, Virginia, Moscoso, Alexis, Grothe, Michel J., Reynés-Llompart, Gabriel, Rodríguez Bel, Laura, Gascón-Bayarri, Jordi, Sobrido, María Jesús, Aguiar, Pablo
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/221340
Acceso en línea:https://hdl.handle.net/2445/221340
Access Level:acceso abierto
Palabra clave:Malalties de Niemann-Pick
Fisiologia patològica
Niemann-Pick diseases
Pathological physiology
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spelling Hypometabolism and atrophy patterns associated with Niemann-Pick type CSilva-Rodríguez, JesúsCastro, CristinaCortés, JuliaArias, ManuelPubul, VirginiaMoscoso, AlexisGrothe, Michel J.Reynés-Llompart, GabrielRodríguez Bel, LauraGascón-Bayarri, JordiSobrido, María JesúsAguiar, PabloMalalties de Niemann-PickFisiologia patològicaNiemann-Pick diseasesPathological physiologyBackground Niemann-Pick disease type C (NP-C) is a rare genetic lysosomal lipid storage disorder characterized by progressive neurological impairment. Early diagnosis is critical for initiating treatment with miglustat, which can decelerate disease progression. In this study, we evaluated a cohort of 22 NP-C patients who underwent MRI, [F-18]FDG PET, and clinical assessment at baseline. We performed a cross-sectional and longitudinal imaging study evaluating the role of [F-18]FDG PET as an adjunct diagnostic tool for NP-C alongside MRI, the current neuroimaging standard. Results Group-level MRI analysis identified significant cerebellar and thalamic atrophy (d = 1.56, p < 0.0001 and d = 1.09, p < 0.001, respectively), with less pronounced involvement of the frontal lobe and hippocampus, which aligned with existing neuropathological understanding and guidelines. Conversely, [F-18]FDG PET imaging revealed extensive hypometabolism in the cerebellum, thalamus, and cingulate cortex (d = 1.42, p < 0.0001), and moderate hypometabolism in broad frontotemporal areas. [F-18]FDG PET provided higher effect sizes across all brain regions, including regions without apparent atrophy, which suggests that it may be more sensitive than MRI for detecting NP-C neurodegenerative changes. Single-subject visual assessment of individual PET images further validated the clinical utility of [F-18]FDG PET, with significant hypometabolism observed in the cerebellum, thalamus and anterior and posterior cingulate reported by physicians in 17/22 patients. Both hypometabolism and atrophy in the cerebellum were associated with ataxia, (more strongly indicated by [F-18]FDG PET, p < 0.0001 vs. MRI, p = 0.07). Medial temporal lobe atrophy was associated with cognitive impairment (p < 0.05), and frontal hypometabolism was slightly related to behavioural impairment (p < 0.07). Longitudinal [F-18]FDG PET analysis revealed progressive subcortical, cortical and cerebellar hypometabolism, which was most pronounced in the cerebellum (-12% per year, p < 0.001). Patients treated with miglustat showed a trend towards attenuated cerebellar hypometabolism progression compared to untreated patients (p = 0.10). Conclusions Our findings delineate a discernible hypometabolism pattern specific to NP-C that distinguishes it from other neurodegenerative conditions, thus suggesting that [F-18]FDG PET might be a promising tool for NP-C diagnosis and to study disease progression.Springer Science and Business Media LLC2025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/221340Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1186/s13550-025-01208-8EJNMMI Research, 2025, vol. 15https://doi.org/10.1186/s13550-025-01208-8cc-by (c) Silva-Rodríguez, Jesús et al., 2025http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2213402026-05-27T06:46:51Z
dc.title.none.fl_str_mv Hypometabolism and atrophy patterns associated with Niemann-Pick type C
title Hypometabolism and atrophy patterns associated with Niemann-Pick type C
spellingShingle Hypometabolism and atrophy patterns associated with Niemann-Pick type C
Silva-Rodríguez, Jesús
Malalties de Niemann-Pick
Fisiologia patològica
Niemann-Pick diseases
Pathological physiology
title_short Hypometabolism and atrophy patterns associated with Niemann-Pick type C
title_full Hypometabolism and atrophy patterns associated with Niemann-Pick type C
title_fullStr Hypometabolism and atrophy patterns associated with Niemann-Pick type C
title_full_unstemmed Hypometabolism and atrophy patterns associated with Niemann-Pick type C
title_sort Hypometabolism and atrophy patterns associated with Niemann-Pick type C
dc.creator.none.fl_str_mv Silva-Rodríguez, Jesús
Castro, Cristina
Cortés, Julia
Arias, Manuel
Pubul, Virginia
Moscoso, Alexis
Grothe, Michel J.
Reynés-Llompart, Gabriel
Rodríguez Bel, Laura
Gascón-Bayarri, Jordi
Sobrido, María Jesús
Aguiar, Pablo
author Silva-Rodríguez, Jesús
author_facet Silva-Rodríguez, Jesús
Castro, Cristina
Cortés, Julia
Arias, Manuel
Pubul, Virginia
Moscoso, Alexis
Grothe, Michel J.
Reynés-Llompart, Gabriel
Rodríguez Bel, Laura
Gascón-Bayarri, Jordi
Sobrido, María Jesús
Aguiar, Pablo
author_role author
author2 Castro, Cristina
Cortés, Julia
Arias, Manuel
Pubul, Virginia
Moscoso, Alexis
Grothe, Michel J.
Reynés-Llompart, Gabriel
Rodríguez Bel, Laura
Gascón-Bayarri, Jordi
Sobrido, María Jesús
Aguiar, Pablo
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Malalties de Niemann-Pick
Fisiologia patològica
Niemann-Pick diseases
Pathological physiology
topic Malalties de Niemann-Pick
Fisiologia patològica
Niemann-Pick diseases
Pathological physiology
description Background Niemann-Pick disease type C (NP-C) is a rare genetic lysosomal lipid storage disorder characterized by progressive neurological impairment. Early diagnosis is critical for initiating treatment with miglustat, which can decelerate disease progression. In this study, we evaluated a cohort of 22 NP-C patients who underwent MRI, [F-18]FDG PET, and clinical assessment at baseline. We performed a cross-sectional and longitudinal imaging study evaluating the role of [F-18]FDG PET as an adjunct diagnostic tool for NP-C alongside MRI, the current neuroimaging standard. Results Group-level MRI analysis identified significant cerebellar and thalamic atrophy (d = 1.56, p < 0.0001 and d = 1.09, p < 0.001, respectively), with less pronounced involvement of the frontal lobe and hippocampus, which aligned with existing neuropathological understanding and guidelines. Conversely, [F-18]FDG PET imaging revealed extensive hypometabolism in the cerebellum, thalamus, and cingulate cortex (d = 1.42, p < 0.0001), and moderate hypometabolism in broad frontotemporal areas. [F-18]FDG PET provided higher effect sizes across all brain regions, including regions without apparent atrophy, which suggests that it may be more sensitive than MRI for detecting NP-C neurodegenerative changes. Single-subject visual assessment of individual PET images further validated the clinical utility of [F-18]FDG PET, with significant hypometabolism observed in the cerebellum, thalamus and anterior and posterior cingulate reported by physicians in 17/22 patients. Both hypometabolism and atrophy in the cerebellum were associated with ataxia, (more strongly indicated by [F-18]FDG PET, p < 0.0001 vs. MRI, p = 0.07). Medial temporal lobe atrophy was associated with cognitive impairment (p < 0.05), and frontal hypometabolism was slightly related to behavioural impairment (p < 0.07). Longitudinal [F-18]FDG PET analysis revealed progressive subcortical, cortical and cerebellar hypometabolism, which was most pronounced in the cerebellum (-12% per year, p < 0.001). Patients treated with miglustat showed a trend towards attenuated cerebellar hypometabolism progression compared to untreated patients (p = 0.10). Conclusions Our findings delineate a discernible hypometabolism pattern specific to NP-C that distinguishes it from other neurodegenerative conditions, thus suggesting that [F-18]FDG PET might be a promising tool for NP-C diagnosis and to study disease progression.
publishDate 2025
dc.date.none.fl_str_mv 2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/221340
url https://hdl.handle.net/2445/221340
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1186/s13550-025-01208-8
EJNMMI Research, 2025, vol. 15
https://doi.org/10.1186/s13550-025-01208-8
dc.rights.none.fl_str_mv cc-by (c) Silva-Rodríguez, Jesús et al., 2025
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Silva-Rodríguez, Jesús et al., 2025
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Springer Science and Business Media LLC
publisher.none.fl_str_mv Springer Science and Business Media LLC
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.81155

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