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

Authors

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

Journal

European Journal Of Nuclear Medicine And Molecular Imaging, Volume: 36, No.: 7, Pages.: 1113-1120

Year of Publication

2009

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 (18)F-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.;

Bibtex Citation

@article{Squitieri_2009, doi = {10.1007/s00259-009-1103-3}, url = {http://dx.doi.org/10.1007/s00259-009-1103-3}, year = 2009, month = {mar}, publisher = {Springer Science $mathplus$ Business Media}, volume = {36}, number = {7}, pages = {1113--1120}, author = {Ferdinando Squitieri and Sara Orobello and Milena Cannella and Tiziana Martino and Pantaleo Romanelli and Giampiero Giovacchini and Luigi Frati and Luigi Mansi and Andrea Ciarmiello}, title = {Riluzole protects Huntington disease patients from brain glucose hypometabolism and grey matter volume loss and increases production of neurotrophins}, journal = {European Journal of Nuclear Medicine and Molecular Imaging} }

Keywords

adult, aged, biological markers, biosynthesis, blood, brain, diagnostic use, drug effects, drug therapy, fluorodeoxyglucose f18, glucose, humans, huntington disease, linear models, magnetic resonance imaging, male, metabolism, middle aged, nerve growth factors, pathology, pharmacology, placebos, radionuclide imaging, riluzole, therapeutic use

Countries of Study

Italy

Types of Dementia

Huntingtons

Types of Study

Randomised Controlled Trial

Type of Outcomes

Physical Health

Type of Interventions

Pharmaceutical Interventions

Pharmaceutical Interventions

Other