Back to Search
Start Over
Progression of structural neuropathology in preclinical Huntington's disease: a tensor based morphometry study.
- Source :
-
Journal of neurology, neurosurgery, and psychiatry [J Neurol Neurosurg Psychiatry] 2005 May; Vol. 76 (5), pp. 650-5. - Publication Year :
- 2005
-
Abstract
- Background and Objectives: Regional cerebral atrophy occurs in carriers of the Huntington's disease (HD) gene mutation before clinical diagnosis is possible. The current inability to reliably measure progression of pathology in this preclinical phase impedes development of therapies to delay clinical onset. We hypothesised that longitudinal statistical imaging would detect progression of structural pathology in preclinical carriers of the HD gene mutation, in the absence of measurable clinical change.<br />Methods: Thirty subjects (17 preclinical mutation positive, 13 mutation negative) underwent serial clinical and magnetic resonance imaging (MRI) assessments over an interval of 2 years. Statistically significant changes in regional grey and white matter volume on MRI were analysed using tensor based morphometry (TBM). This technique derives a voxel-wise estimation of regional tissue volume change from the deformation field required to warp a subject's early to late T1 images.<br />Results: Over 2 years, there was progressive regional grey matter atrophy in mutation-positive relative to negative subjects, without significant clinical progression of disease. Significant grey matter volume loss was limited to bilateral putamen and globus pallidus externa (GPe), left caudate nucleus, and left ventral midbrain in the region of the substantia nigra.<br />Conclusions: While these results are consistent with previous cross sectional pathologic and morphometric studies, significant progression of atrophy in HD before the onset of significant clinical decline is now demonstrable with longitudinal statistical imaging. Such measures could be used to assess the efficacy of potential disease modifying drugs in slowing the progression of pathology before confirmed clinical onset of HD.
- Subjects :
- Adult
Atrophy pathology
Caudate Nucleus pathology
Disease Progression
Female
Follow-Up Studies
Globus Pallidus pathology
Humans
Huntington Disease epidemiology
Huntington Disease genetics
Incidence
Magnetic Resonance Imaging
Male
Mesencephalon pathology
Point Mutation genetics
Putamen pathology
Substantia Nigra pathology
Trinucleotide Repeats genetics
Brain pathology
Huntington Disease pathology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-3050
- Volume :
- 76
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of neurology, neurosurgery, and psychiatry
- Publication Type :
- Academic Journal
- Accession number :
- 15834021
- Full Text :
- https://doi.org/10.1136/jnnp.2004.047993