Chang et al. BMC Neurology 2010, 10:59 http://www.biomedcentral.com/1471-2377/10/59 Open Access RESEARCH ARTICLE © 2010 Chang et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Research article Multi-parametric neuroimaging evaluation of cerebrotendinous xanthomatosis and its correlation with neuropsychological presentations Chiung-Chih Chang 1 , Chun-Chung Lui 2 , Jiun-Jie Wang 3 , Shu-Hua Huang 4 , Cheng-Hsien Lu 1 , Ching Chen 5 , Chih- Feng Chen 2 , Min-Chien Tu 1 , Chi-Wei Huang 1 and Wen-Neng Chang* 1 Abstract Background: Cerebrotendinous xanthomatosis (CTX) is a rare genetic disorder. Recent studies show that brain damage in CTX patients extends beyond the abnormalities observed on conventional magnetic resonance imaging (MRI). We studied the MRI and 99 m Tc-ethyl cysteinate dimer single photon emission computed tomography (SPECT) findings of CTX patients and made a correlation with the neuropsychological presentations. Methods: Diffusion tensor imaging (DTI) and 3D T1-weighted images of five CTX patients were compared with 15 age- matched controls. Voxel-based morphometry (VBM) was use to delineate gray matter (GM) and white matter (WM) volume loss. Fractional anisotropy (FA), mean diffusivity (MD), and eigenvalues derived from DTI were used to detect WM changes and correlate with neuropsychological results. SPECT functional studies were used to correlate with GM changes. Results: Cognitive results showed that aside from moderate mental retardation, the patient group performed worse in all cognitive domains. Despite the extensive GM atrophy pattern, the cerebellum, peri-Sylvian regions and parietal- occipital regions were correlated with SPECT results. WM atrophy located in the peri-dentate and left cerebral peduncle areas corresponded with changes in diffusion measures, while axial and radial diffusivity suggested both demyelinating and axonal changes. Changes in FA and MD were preceded by VBM in the corpus callosum and corona radiata. Cognitive results correlated with FA changes. Conclusion: In CTX, GM atrophy affected the perfusion patterns. Changes in WM included atrophy, and axonal changes with demyelination. Disconnection of major fiber tracts among different cortical regions may contribute to cognitive impairment. Backgroud Cerebrotendinous xanthomatosis (CTX) is a rare, auto- somal recessive, lipid storage disease. Leukoencephalopa- thy, signal abnormalities of dentate nuclei of the cerebellum, is frequently reported in conventional brain magnetic resonance imaging (MRI) [1]. Recent studies have shown that brain damage in CTX patients extends well beyond the abnormalities observed on conventional neuroimaging studies [1], and that this maybe responsible for the neurologic manifestations. Voxel-based morphometry (VBM) is an unbiased, whole brain quantitative method that can detect atro- phies of gray matter (GM) and white matter (WM) [2]. Diffusion tensor imaging (DTI) can be used to investigate WM tract pathology since it is sensitive to water diffusion [2]. Fractional anisotropy (FA) and mean diffusivity (MD) [3] can be derived from DTI to provide information on micro-structural changes. FA is a reflection of the degree of directionality of cellular structures within the fiber tracts [4,5], while MD represents the magnitude of diffu- sion and reveals information on tissue integrity [6]. Anal- yses of axial and radial diffusivities provide potential measures of the mechanisms that underlie diffusion ten- sor changes. Tract-based spatial statistics (TBSS) focuses * Correspondence: cwenneng@ms19.hinet.net 1 Department of Neurology, Chang Gung Memorial Hospital-Kaohsiung Medical Center and Chang Gung University College of Medicine, 123, Ta-Pei Road, Niaosung, Kaohsiung County 833, Taiwan Full list of author information is available at the end of the article