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18F-FDG PET uptake in the pre-Huntington disease caudate affects the time-to-onset independently of CAG expansion size

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

Abstract

Purpose

To test in a longitudinal follow-up study whether basal glucose metabolism in subjects with a genetic risk of Huntington disease (HD) may influence the onset of manifest symptoms.

Methods

The study group comprised 43 presymptomatic (preHD) subjects carrying the HD mutation. They underwent a 18F-FDG PET scan and were prospectively followed-up for at least 5 years using the unified HD rating scale to detect clinical changes. Multiple regression analysis included subject’s age, CAG mutation size and glucose uptake as variables in a model to predict age at onset.

Results

Of the 43 preHD subjects who manifested motor symptoms, suggestive of HD, after 5 years from the PET scan, 26 showed a mean brain glucose uptake below the cut-off of 1.0493 in the caudate, significantly lower than the 17 preHD subjects who remained symptom-free (P < 0.0001). This difference was independent of mutation size. Measurement of brain glucose uptake improved the CAG repeat number and age-based model for predicting age at onset by 37 %.

Conclusion

A reduced level of glucose metabolism in the brain caudate may represent a predisposing factor that contributes to the age at onset of HD in preHD subjects, in addition to the mutation size.

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Acknowledgments

We are grateful for the support of the Italian association of HD families 'Associazione-Italiana-Corea-di-Huntington-Neuromed' (funds from 5x1000, to F.S.), IRCCS Neuromed (institutional funds from 5x1000 to F.S. and S.O.), Ministry of Health, Italy (Ricerca Corrente, to F.S.), Italian Olympic Committee (CONI, to E.F.), and of the European Huntington’s Disease Network for the REGISTRY Study (to F.S., E.F. and S.O.).

Conflicts of interest

None.

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Authors and Affiliations

  1. Nuclear Medicine Department, S. Andrea Hospital, via Vittorio Veneto, 197, La Spezia, Italy

    Andrea Ciarmiello, Giampiero Giovacchini & Laura Bruselli

  2. Centre for Neurogenetics and Rare Diseases, IRCCS Neuromed, Località Camerelle, Pozzilli, IS, Italy

    Sara Orobello, Francesca Elifani & Ferdinando Squitieri

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  1. Andrea Ciarmiello
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  2. Giampiero Giovacchini
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  4. Laura Bruselli
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  6. Ferdinando Squitieri
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Correspondence to Andrea Ciarmiello or Ferdinando Squitieri.

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Ciarmiello, A., Giovacchini, G., Orobello, S. et al. 18F-FDG PET uptake in the pre-Huntington disease caudate affects the time-to-onset independently of CAG expansion size. Eur J Nucl Med Mol Imaging 39, 1030–1036 (2012). https://doi.org/10.1007/s00259-012-2114-z

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  • DOI: https://doi.org/10.1007/s00259-012-2114-z

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