Multi-parametric neuroimaging evaluation of cerebrotendinous xanthomatosis and its correlation with neuropsychological presentations.
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 mTc-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.


CONCLUSIONS
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.
Chang
Chiung-Chih
CC
Department of Neurology, Chang Gung Memorial Hospital-Kaohsiung Medical Center and Chang Gung University College of Medicine, Niaosung, Taiwan.
Lui
Chun-Chung
CC
Wang
Jiun-Jie
JJ
Huang
Shu-Hua
SH
Lu
Cheng-Hsien
CH
Chen
Ching
C
Chen
Chih-Feng
CF
Tu
Min-Chien
MC
Huang
Chi-Wei
CW
Chang
Wen-Neng
WN
D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology*; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000000981:diagnostic imaging / Q000473:pathology*; D003545:Cysteine / Q000031:analogs & derivatives; D056324:Diffusion Tensor Imaging; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional; D008607:Intellectual Disability / Q000000981:diagnostic imaging / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D015609:Organotechnetium Compounds; D015899:Tomography, Emission-Computed, Single-Photon; D019294:Xanthomatosis, Cerebrotendinous / Q000000981:diagnostic imaging / Q000473:pathology*
D015609:Organotechnetium Compounds; C059659:technetium Tc 99m bicisate; D003545:Cysteine