Clinical Neuroscience

[Diffusion MRI measured white matter microstructure as a biomarker of neurodegeneration in preclinical Huntington’s disease]

KINCSES Tamás Zsigmond1,2, SZABÓ Nikoletta2,1, TÓTH Eszter3,1, ZÁDORI Dénes1, FARAGÓ Péter1, NÉMETH Dezsõ4, JANACSEK Karolina4, BABOS Magor5, KLIVÉNYI Péter1, VÉCSEI László6,1

NOVEMBER 30, 2013

Clinical Neuroscience - 2013;66(11-12)

[Background - Huntington’s disease is a progressive neurodegenerative disease, genetically determined by CAG trinucleotide expansions in the IT15 gene. The onset of the symptoms is related to the number of CAG triplets. Because the patients are asymptomatic in the early phase of the disease, in vivo biomarkers are needed to follow up the neurodegeneration and to test putative neuroprotective approaches. One such promising biomarker is the diffusion MRI measured microstructural alteration of the white matter. Methods - Seven presymtomatic, mutation carriers and ten age-matched healthy controls were included in the study. Diffusion parameters were compared between groups and correlated with measures describing neurodegeneration. In order to reduce the possible misregistration bias due to atrophy the analysis was restricted to the core of each fibre bundles as defined by maximal fractional anisotropy (Tract- Based Spatial Statistics). Results - Decreased fractional anisotropy, along with increased mean, parallel and perpendicular diffusivity was found in white matter tracts, mainly in the corpus callosum. An inverse correlation was detected between the fractional anisotropy and neurodegeneration score (derived from the number of CAG triplets and the patient age) from the areas of the left precentral gyrus, frontal lobe, corpus callosum and the capsula extrema. Altered diffusion parameters are promising biomarkers of the neurodegeneration in Huntington’s disease.]


  1. Department of Neurology, Albert Szent-Györgyi Clinical Center, University of Szeged, Szeged
  2. International Clinical Research Center, St. Anne’s University Hospital, Brno, Czech Republic
  3. International Clinical Research Center, St. Anne’s University Hospital Brno, Brno, Czech Republic
  4. Department of Clinical Psychology and Addiction, Institute of Psychology, Eötvös Loránd University, Budapest
  5. Euromedic Hungary Ltd., Szeged
  6. Neuroscience Research Group of the Hungarian Academy of Sciences and University of Szeged



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Background - Huntington’s disease is a progressive disease in which neurodegeneration is on-going from the early presymptomatic phase. Development of sensitive biomarkers in this presymptomatic stage that are able to monitor the disease progression and test the efficacy of putative neuroprotective treatments are essential. Methods - Seven presymptomatic Huntington mutation carriers and ten age-matched healthy controls were recruited. Six of the patients participated in a 24 months longitudinal study having MRI scans 12 and 24 months after the baseline measurements. High resolution T1 weighted images were carried out and voxel based morphometry was used to analyse the data. Apart of group differences, correlation of CAG repeat number with focal cortical thickness and with global gray matter volume was calculated. Results - Focal cortical atrophy was found bilaterally in the superior temporal sulcus and in the left middle frontal gyrus in presymptomatic Huntington patients in whom no sign of cognitive or motor deterioration was detected. Global gray matter atrophy (p<0.048) and decreased total brain volume was found. The number of CAG triplets showed no correlation with the focal gray matter atrophy and total brain volume. Strong correlation between the CAG repeat number and global gray matter volume was found (p<0.016). Conclusion - Cortical atrophy is apparent in the early, presymptomatic stage of the disease. With further validation in large patient sample atrophy measure could be biomarker of disease progression and putatively of neurodegeneration.

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