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Striatal hypometabolism in premanifest and manifest Huntington’s disease patients

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

To assess metabolic changes in cerebral 18F-FDG PET/CT in premanifest and manifest Huntington’s disease (HD) subjects compared to a control group and to correlate 18F-FDG uptake patterns with different disease stages.

Materials and methods

Thirty-three gene-expanded carriers (Eight males; mean age: 43 y/o; CAG > 39) were prospectively included. Based on the Unified Huntington’s Disease Rating Scale Total Motor Score and the Total Functional Capacity, subjects were classified as premanifest (preHD = 15) and manifest (mHD = 18). Estimated time disease-onset was calculated using the Langbehn formula, which allowed classifying preHD as far-to (preHD-A) and close-to (PreHD-B) disease-onset. Eighteen properly matched participants were included as a control group (CG). All subjects underwent brain 18F-FDG PET/CT and MRI. 18F-FDG PET/CT were initially assessed by two nuclear medicine physicians identifying qualitative metabolic changes in the striatum. Quantitative analysis was performed using SPM8 with gray matter atrophy correction using the BPM toolbox.

Results

Visual analysis showed a marked striatal hypometabolism in mHD. A normal striatal distribution of 18F-FDG uptake was observed for most of the preHD subjects. Quantitative analysis showed a significant striatal hypometabolism in mHD subjects compared to CG (p < 0.001 uncorrected, k = 50 voxels). In both preHD groups we observed a significant striatal hypometabolism with respect to CG (p < 0.001 uncorrected, k = 50 voxels). In mHD subjects we observed a significant striatal hypometabolism with respect to both preHD groups (p < 0.001 uncorrected, k = 50 voxels).

Conclusion

18F-FDG PET/CT might be a helpful tool to identify patterns of glucose metabolism in the striatum across the stages of HD and might be relevant in assessing the clinical status of gene-expanded HD carriers due to the fact that dysfunctional glucose metabolism begins at early preHD stages of the disease. 18F-FDG PET/CT appears as a promising method to monitor the response to disease-modifying therapies even if applied in premanifest subjects.

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Authors and Affiliations

  1. Nuclear Medicine Department, Hospital Sant Pau, Autonomous University of Barcelona, Barcelona, Spain

    Diego Alfonso López-Mora, Valle Camacho, Alejandro Fernández, Alberto Montes & Ignasi Carrió

  2. Movement Disorders Unit, Neurology Department, Hospital Sant Pau, Autonomous University of Barcelona, Barcelona, Spain

    Jesús Pérez-Pérez, Saül Martínez-Horta & Jaime Kulisevsky

  3. University of Barcelona, Barcelona, Spain

    Frederic Sampedro

  4. Neuroradiology, Radiology Department, Hospital Sant Pau, Autonomous University of Barcelona, Barcelona, Spain

    Gloria Andrea Lozano-Martínez & Beatriz Gómez-Anson

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  1. Diego Alfonso López-Mora
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Correspondence to Diego Alfonso López-Mora.

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This study was not funded.

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. All authors declare that they have 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. This article does not contain any studies with animals performed by any of the authors.

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

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López-Mora, D.A., Camacho, V., Pérez-Pérez, J. et al. Striatal hypometabolism in premanifest and manifest Huntington’s disease patients. Eur J Nucl Med Mol Imaging 43, 2183–2189 (2016). https://doi.org/10.1007/s00259-016-3445-y

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  • DOI: https://doi.org/10.1007/s00259-016-3445-y

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