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European Journal of Nuclear Medicine and Molecular Imaging

Erschienen in:

01.07.2009 | Original Article

Riluzole protects Huntington disease patients from brain glucose hypometabolism and grey matter volume loss and increases production of neurotrophins

verfasst von: Ferdinando Squitieri, Sara Orobello, Milena Cannella, Tiziana Martino, Pantaleo Romanelli, Giampiero Giovacchini, Luigi Frati, Luigi Mansi, Andrea Ciarmiello

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 7/2009

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Abstract

Purpose

Huntington disease (HD) mutation increases gain-of-toxic functions contributing to glutamate-mediated excitotoxicity. Riluzole interferes with glutamatergic neurotransmission, thereby reducing excitotoxicity, enhancing neurite formation in damaged motoneurons and increasing serum concentrations of BDNF, a brain cortex neurotrophin protecting striatal neurons from degeneration.

Methods

We investigated metabolic and volumetric differences in distinct brain areas between 11 riluzole-treated and 12 placebo-treated patients by MRI and ¹⁸F-fluoro-2-deoxy-d-glucose (FDG) PET scanning, according to fully automated protocols. We also investigated the influence of riluzole on peripheral growth factor blood levels.

Results

Placebo-treated patients showed significantly greater proportional volume loss of grey matter and decrease in metabolic FDG uptake than patients treated with riluzole in all cortical areas (p<0.05). The decreased rate of metabolic FDG uptake correlated with worsening clinical scores in placebo-treated patients, compared to those who were treated with riluzole. The progressive decrease in metabolic FDG uptake observed in the frontal, parietal and occipital cortex correlated linearly with the severity of motor scores calculated by Unified Huntington Disease Rating Scale (UHDRS-I) in placebo-treated patients. Similarly, the rate of metabolic changes in the frontal and temporal areas of the brain cortex correlated linearly with worsening behavioural scores calculated by UHDRS-III in the placebo-treated patients. Finally, BDNF and transforming growth factor beta-1 serum levels were significantly higher in patients treated with riluzole.

Conclusion

The linear correlation between decreased metabolic FDG uptake and worsening clinical scores in the placebo-treated patients suggests that FDG-PET may be a valuable procedure to assess brain markers of HD.

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Titel: Riluzole protects Huntington disease patients from brain glucose hypometabolism and grey matter volume loss and increases production of neurotrophins
verfasst von: Ferdinando Squitieri
Sara Orobello
Milena Cannella
Tiziana Martino
Pantaleo Romanelli
Giampiero Giovacchini
Luigi Frati
Luigi Mansi
Andrea Ciarmiello
Publikationsdatum: 01.07.2009
Verlag: Springer-Verlag
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 7/2009
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-009-1103-3

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

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