nach oben

European Journal of Nuclear Medicine and Molecular Imaging

Erschienen in:

01.06.2012 | Original Article

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

verfasst von: Andrea Ciarmiello, Giampiero Giovacchini, Sara Orobello, Laura Bruselli, Francesca Elifani, Ferdinando Squitieri

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 6/2012

Einloggen, um Zugang zu erhalten

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.

Grafton ST, Mazziotta JC, Pahl JJ, St George-Hyslop P, Haines JL, Gusella J, et al. Serial changes of cerebral glucose metabolism and caudate size in persons at risk for Huntington's disease. Arch Neurol. 1992;49:1161–7.PubMedCrossRef

Kuwert T, Lange HW, Boecker H, Titz H, Herzog H, Aulich A, et al. Striatal glucose consumption in chorea-free subjects at risk of Huntington's disease. J Neurol. 1993;241:31–6.PubMedCrossRef

Antonini A, Leenders KL, Spiegel R, Meier D, Vontobel P, Weigell-Weber M, et al. Striatal glucose metabolism and dopamine D2 receptor binding in asymptomatic gene carriers and patients with Huntington's disease. Brain. 1996;119(Pt 6):2085–95.PubMedCrossRef

Feigin A, Fukuda M, Dhawan V, Przedborski S, Jackson-Lewis V, Mentis MJ, et al. Metabolic correlates of levodopa response in Parkinson's disease. Neurology. 2001;57:2083–8.PubMed

Ciarmiello A, Cannella M, Lastoria S, Simonelli M, Frati L, Rubinsztein DC, et al. Brain white-matter volume loss and glucose hypometabolism precede the clinical symptoms of Huntington's disease. J Nucl Med. 2006;47:215–22.PubMed

Brinkman RR, Mezei MM, Theilmann J, Almqvist E, Hayden MR. The likelihood of being affected with Huntington disease by a particular age, for a specific CAG size. Am J Hum Genet. 1997;60:1202–10.PubMed

Squitieri F, Sabbadini G, Mandich P, Gellera C, Di Maria E, Bellone E, et al. Family and molecular data for a fine analysis of age at onset in Huntington disease. Am J Med Genet. 2000;95:366–73.PubMedCrossRef

Langbehn DR, Brinkman RR, Falush D, Paulsen JS, Hayden MR. A new model for prediction of the age of onset and penetrance for Huntington's disease based on CAG length. Clin Genet. 2004;65:267–77. doi:10.1111/j.1399-0004.2004.00241.x.PubMedCrossRef

Rubinsztein DC, Leggo J, Coles R, Almqvist E, Biancalana V, Cassiman JJ, et al. Phenotypic characterization of individuals with 30-40 CAG repeats in the Huntington disease (HD) gene reveals HD cases with 36 repeats and apparently normal elderly individuals with 36-39 repeats. Am J Hum Genet. 1996;59:16–22.PubMed

10.

Wexler NS, Lorimer J, Porter J, Gomez F, Moskowitz C, Shackell E, et al. Venezuelan kindreds reveal that genetic and environmental factors modulate Huntington's disease age of onset. Proc Natl Acad Sci U S A. 2004;101:3498–503. doi:10.1073/pnas.0308679101.PubMedCrossRef

11.

Esmaeilzadeh M, Ciarmiello A, Squitieri F. Seeking brain biomarkers for preventive therapy in Huntington disease. CNS Neurosci Ther. 2011;17:368–86. doi:10.1111/j.1755-5949.2010.00157.x.PubMedCrossRef

12.

Penney Jr JB, Young AB, Shoulson I, Starosta-Rubenstein S, Snodgrass SR, Sanchez-Ramos J, et al. Huntington's disease in Venezuela: 7 years of follow-up on symptomatic and asymptomatic individuals. Mov Disord. 1990;5:93–9.PubMedCrossRef

13.

Lynoe N, Sandlund M, Dahlqvist G, Jacobsson L. Informed consent: study of quality of information given to participants in a clinical trial. BMJ. 1991;303:610–3.PubMedCrossRef

14.

Huntington Study Group. Unified Huntington's disease rating scale: reliability and consistency. Mov Disord. 1996;11:136–42.CrossRef

15.

Squitieri F, Gellera C, Cannella M, Mariotti C, Cislaghi G, Rubinsztein DC, et al. Homozygosity for CAG mutation in Huntington disease is associated with a more severe clinical course. Brain. 2003;126:946–55.PubMedCrossRef

16.

Alfano B, Brunetti A, Covelli EM, Quarantelli M, Panico MR, Ciarmiello A, et al. Unsupervised, automated segmentation of the normal brain using a multispectral relaxometric magnetic resonance approach. Magn Reson Med. 1997;37:84–93.PubMedCrossRef

17.

Quarantelli M, Berkouk K, Prinster A, Landeau B, Svarer C, Balkay L, et al. Integrated software for the analysis of brain PET/SPECT studies with partial-volume-effect correction. J Nucl Med. 2004;45:192–201.PubMed

18.

Muller-Gartner HW, Links JM, Prince JL, Bryan RN, McVeigh E, Leal JP, et al. Measurement of radiotracer concentration in brain gray matter using positron emission tomography: MRI-based correction for partial volume effects. J Cereb Blood Flow Metab. 1992;12:571–83. doi:10.1038/jcbfm.1992.81.PubMedCrossRef

19.

Rousset OG, Ma Y, Evans AC. Correction for partial volume effects in PET: principle and validation. J Nucl Med. 1998;39:904–11.PubMed

20.

Minoshima S, Frey KA, Foster NL, Kuhl DE. Preserved pontine glucose metabolism in Alzheimer disease: a reference region for functional brain image (PET) analysis. J Comput Assist Tomogr. 1995;19:541–7.PubMedCrossRef

21.

Brickman AM, Buchsbaum MS, Shihabuddin L, Hazlett EA, Borod JC, Mohs RC. Striatal size, glucose metabolic rate, and verbal learning in normal aging. Brain Res Cogn Brain Res. 2003;17:106–16.PubMedCrossRef

22.

Petit-Taboue MC, Landeau B, Desson JF, Desgranges B, Baron JC. Effects of healthy aging on the regional cerebral metabolic rate of glucose assessed with statistical parametric mapping. Neuroimage. 1998;7:176–84. doi:10.1006/nimg.1997.0318.PubMedCrossRef

23.

Hanley JA, McNeil BJ. The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology. 1982;143:29–36.PubMed

24.

Tabrizi SJ, Langbehn DR, Leavitt BR, Roos RA, Durr A, Craufurd D, et al. Biological and clinical manifestations of Huntington's disease in the longitudinal TRACK-HD study: cross-sectional analysis of baseline data. Lancet Neurol. 2009;8:791–801. doi:10.1016/S1474-4422(09)70170-X.PubMedCrossRef

25.

Yamamoto A, Lucas JJ, Hen R. Reversal of neuropathology and motor dysfunction in a conditional model of Huntington's disease. Cell. 2000;101:57–66. doi:10.1016/S0092-8674(00)80623-6.PubMedCrossRef

26.

Aylward EH, Sparks BF, Field KM, Yallapragada V, Shpritz BD, Rosenblatt A, et al. Onset and rate of striatal atrophy in preclinical Huntington disease. Neurology. 2004;63:66–72.PubMed

27.

Ruocco HH, Bonilha L, Li LM, Lopes-Cendes I, Cendes F. Longitudinal analysis of regional grey matter loss in Huntington disease: effects of the length of the expanded CAG repeat. J Neurol Neurosurg Psychiatry. 2008;79:130–5. doi:10.1136/jnnp.2007.116244.PubMedCrossRef

28.

Squitieri F, Cannella M, Simonelli M, Sassone J, Martino T, Venditti E, et al. Distinct brain volume changes correlating with clinical stage, disease progression rate, mutation size, and age at onset prediction as early biomarkers of brain atrophy in Huntington's disease. CNS Neurosci Ther. 2009;15:1–11. doi:10.1111/j.1755-5949.2008.00068.x.PubMedCrossRef

29.

Powers WJ, Videen TO, Markham J, McGee-Minnich L, Antenor-Dorsey JV, Hershey T, et al. Selective defect of in vivo glycolysis in early Huntington's disease striatum. Proc Natl Acad Sci U S A. 2007;104(8):2945–9. doi:10.1073/pnas.0609833104.PubMedCrossRef

30.

Shin JY, Fang ZH, Yu ZX, Wang CE, Li SH, Li XJ. Expression of mutant huntingtin in glial cells contributes to neuronal excitotoxicity. J Cell Biol. 2005;171:1001–12. doi:10.1083/jcb.200508072.PubMedCrossRef

31.

Li H, Li SH, Yu ZX, Shelbourne P, Li XJ. Huntingtin aggregate-associated axonal degeneration is an early pathological event in Huntington's disease mice. J Neurosci. 2001;21:8473–81.PubMed

32.

Gauthier LR, Charrin BC, Borrell-Pages M, Dompierre JP, Rangone H, Cordelieres FP, et al. Huntingtin controls neurotrophic support and survival of neurons by enhancing BDNF vesicular transport along microtubules. Cell. 2004;118:127–38. doi:10.1016/j.cell.2004.06.018.PubMedCrossRef

33.

Battaglia G, Cannella M, Riozzi B, Orobello S, Maat-Schieman ML, Aronica E, et al. Early defect of transforming growth factor beta1 formation in Huntington's disease. J Cell Mol Med. 2011;15:555–71. doi:10.1111/j.1582-4934.2010.01011.x.PubMedCrossRef

34.

Gonitel R, Moffitt H, Sathasivam K, Woodman B, Detloff PJ, Faull RL, et al. DNA instability in postmitotic neurons. Proc Natl Acad Sci U S A. 2008;105:3467–72. doi:10.1073/pnas.0800048105.PubMedCrossRef

35.

Cannella M, Maglione V, Martino T, Ragona G, Frati L, Li GM, et al. DNA instability in replicating Huntington's disease lymphoblasts. BMC Med Genet. 2009;10:11. doi:10.1186/1471-2350-10-11.PubMedCrossRef

36.

Swami M, Hendricks AE, Gillis T, Massood T, Mysore J, Myers RH, et al. Somatic expansion of the Huntington's disease CAG repeat in the brain is associated with an earlier age of disease onset. Hum Mol Genet. 2009;18:3039–47. doi:10.1093/hmg/ddp242.PubMedCrossRef

37.

Li JL, Hayden MR, Almqvist EW, Brinkman RR, Durr A, Dode C, et al. A genome scan for modifiers of age at onset in Huntington disease: the HD MAPS study. Am J Hum Genet. 2003;73:682–7. doi:10.1086/378133.PubMedCrossRef

Titel: 18F-FDG PET uptake in the pre-Huntington disease caudate affects the time-to-onset independently of CAG expansion size
verfasst von: Andrea Ciarmiello
Giampiero Giovacchini
Sara Orobello
Laura Bruselli
Francesca Elifani
Ferdinando Squitieri
Publikationsdatum: 01.06.2012
Verlag: Springer-Verlag
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 6/2012
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-012-2114-z

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 6/2012

Comparison of 11C-PiB and 18F-florbetaben for Aβ imaging in ageing and Alzheimer’s disease

Whole-body metabolic tumour volume of 18F-FDG PET/CT improves the prediction of prognosis in small cell lung cancer

Feasibility of bremsstrahlung dosimetry for direct dose estimation in patients undergoing treatment with 90Y-ibritumomab tiuxetan

Longitudinal imaging of Alzheimer pathology using [11C]PIB, [18F]FDDNP and [18F]FDG PET

Relationship between late ventricular potentials and myocardial 123I-metaiodobenzylguanidine scintigraphy in patients with dilated cardiomyopathy with mild to moderate heart failure: results of a prospective study of sudden death events

Correction of an important typographical error in the European Association of Nuclear Medicine (EANM) guidelines