| Riluzole protects Huntington disease patients from brain glucose hypometabolism and grey matter volume loss and increases production of neurotrophins. | |
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MedLine Citation:
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PMID: 19280185 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Ferdinando Squitieri; Sara Orobello; Milena Cannella; Tiziana Martino; Pantaleo Romanelli; Giampiero Giovacchini; Luigi Frati; Luigi Mansi; Andrea Ciarmiello |
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Publication Detail:
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Type: Controlled Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't Date: 2009-03-11 |
Journal Detail:
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Title: European journal of nuclear medicine and molecular imaging Volume: 36 ISSN: 1619-7089 ISO Abbreviation: Eur. J. Nucl. Med. Mol. Imaging Publication Date: 2009 Jul |
Date Detail:
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Created Date: 2009-06-05 Completed Date: 2009-08-13 Revised Date: 2011-11-24 |
Medline Journal Info:
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Nlm Unique ID: 101140988 Medline TA: Eur J Nucl Med Mol Imaging Country: Germany |
Other Details:
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Languages: eng Pagination: 1113-20 Citation Subset: IM |
Affiliation:
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Neurogenetics Unit & Centre for Rare Disease, IRCCS Neuromed, Località Camerelle, 86077, Pozzilli, Italy. squitieri@neuromed.it |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Biological Markers / blood Brain / drug effects*, metabolism*, pathology, radionuclide imaging Fluorodeoxyglucose F18 / diagnostic use Glucose / metabolism* Humans Huntington Disease / blood, drug therapy, metabolism*, pathology* Linear Models Magnetic Resonance Imaging Male Middle Aged Nerve Growth Factors / biosynthesis*, blood Placebos Positron-Emission Tomography Riluzole / pharmacology*, therapeutic use |
| Grant Support | |
ID/Acronym/Agency:
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GGP06181//Telethon |
| Chemical | |
Reg. No./Substance:
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0/Biological Markers; 0/Nerve Growth Factors; 0/Placebos; 1744-22-5/Riluzole; 50-99-7/Glucose; 63503-12-8/Fluorodeoxyglucose F18 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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