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Cortical atrophic-hypometabolic dissociation in the transition from premanifest to early-stage Huntington’s disease

  • Frederic Sampedro
  • Saul Martínez-Horta
  • Jesús Perez-Perez
  • Andrea Horta-Barba
  • Diego Alfonso Lopez-Mora
  • Valle Camacho
  • Alejandro Fernández-León
  • Beatriz Gomez-Anson
  • Ignasi Carrió
  • Jaime KulisevskyEmail author
Original Article
  • 37 Downloads

Abstract

Purpose

Huntington’s disease (HD) is a fatal neurodegenerative disorder with no effective treatment currently available. Although the pathological hallmark of HD is massive striatal atrophy, it has been suggested that cortical deterioration may concomitantly occur and play a major role in the patient’s functional independence. Our objective was to characterize cortical structural and metabolic neurodegeneration in the transition from premanifest to early-stage Huntington’s disease (HD).

Methods

Using a surface-based neuroimaging approach, we compared cortical thickness and intracortical FDG-PET uptake in 19 early-symptomatic HD patients with respect to 21 premanifest HD individuals.

Results

Early-HD patients showed significant cortical atrophy and intracortical hypometabolism when compared to premanifest subjects (p < 0.05, corrected for multiple comparisons). However, whereas the atrophy pattern was restricted to precentral and parieto-occipital regions, a pronounced frontotemporal hypometabolism was observed. Importantly, structural changes correlated with motor and cognitive performance, and metabolic changes were associated with the presence and severity of apathy in this population, a core neuropsychiatric feature of this disorder.

Conclusion

Our findings reveal an asynchronous neuronal loss and metabolic compromise across the cerebral cortex in early HD. Hence, the use of structural and metabolic imaging indicators to characterize disease progression in this population should take into consideration the dissociation which occurs between cortical atrophy and hypometabolism.

Keywords

Huntington’s disease 18F-FDG-PET Cortical thickness Partial volume correction 

Notes

Acknowledgements

The authors wish to thank all those at the Hospital de la Santa Creu i Sant Pau involved in the study. The authors also wish to thank the study participants and their families.

Funding

This study was partially funded by a Spanish Government Grant (PI17/001885).

Compliance with ethical standards

Conflict of interest

Author Frederic Sampedro declares that he has no conflict of interest. Author Saul Martínez-Horta declares that he has no conflict of interest. Author Jesus Perez-Perez declares that he has no conflict of interest. Author Andrea Horta-Barba declares that she has no conflict of interest. Author Diego-Alfonso Lopez-Mora declares that he has no conflict of interest. Author Valle Camacho declares that she has no conflict of interest. Author Alejandro Fernandez-Leon declares that he has no conflict of interest. Author Beatriz Gomez-Anson declares that she has no conflict of interest. Author Ignasi Carrió declares that he has no conflict of interest. Author Jaime Kulisevsky declares that he has no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Frederic Sampedro
    • 1
    • 2
    • 3
  • Saul Martínez-Horta
    • 1
    • 2
    • 3
    • 4
  • Jesús Perez-Perez
    • 1
    • 2
    • 3
    • 4
    • 5
  • Andrea Horta-Barba
    • 1
    • 2
    • 4
  • Diego Alfonso Lopez-Mora
    • 6
  • Valle Camacho
    • 6
  • Alejandro Fernández-León
    • 6
  • Beatriz Gomez-Anson
    • 5
    • 7
  • Ignasi Carrió
    • 5
    • 6
  • Jaime Kulisevsky
    • 1
    • 2
    • 3
    • 4
    • 5
    Email author
  1. 1.Movement Disorders Unit, Neurology DepartmentHospital de la Santa Creu i Sant PauBarcelonaSpain
  2. 2.Biomedical Research Institute (IIB-Sant Pau)BarcelonaSpain
  3. 3.Centro de Investigación en Red-Enfermedades Neurodegenerativas (CIBERNED)BarcelonaSpain
  4. 4.European Huntington’s Disease Network (EHDN)UlmGermany
  5. 5.Autonomous University of BarcelonaBarcelonaSpain
  6. 6.Nuclear Medicine DepartmentHospital de la Santa Creu i Sant PauBarcelonaSpain
  7. 7.Neuroradiology, Radiology DepartmentHospital de la Santa Creu i Sant PauBarcelonaSpain

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