Magnetic resonance imaging and spectroscopic changes in brains of patientswith cerebrotendinous xanthomatosis

Cerebrotendinous xanthomatosis (CTX) is a rare disorder due to an inherited defect in the metabolic pathway of cholesterol, Early diagnosis of the dis ease is particularly important as patients benefit from therapy with chenod eoxycholic acid. Although the disease is clinically characterized by the co ncomitant presence of tendon xanthomas, juvenile cataracts and progressive neurological impairment, clinical features may vary greatly. Neuroradiologi cal studies have suggested that the bilateral abnormality of the dentate nu clei could be typical of this disease. However, this finding has been seen inconsistently on conventional MRT, The dynamic of the CNS pathology in CTX is complex, and whether demyelination or axonopathy has primary importance in the pathogenesis of CTX pathology is not known. To clarify both neurora diological and pathological issues, we performed combined brain MRI and spe ctroscopy examinations on 12 CTX patients. On conventional MRIs, bilateral hyperintensities of the dentate nuclei were clearly seen in nine out of 12 patients on T-2-weighted MRIs, but were evident in all patients using a FLA IR sequence. On proton magnetic resonance (MR) spectroscopy, significant de creases in N-acetylaspartate resonance intensities (P < 0.0001) and increas es in lactate MR signals (P < 0.05) were found in the group of CTX patients in large volumes of interest localized above the lateral brain ventricles and in the cerebellar hemispheres. Cerebral values of N-acetylaspartate res onance intensities showed a close correlation with patients' disability (Sp earman rank correlation = -0.78, P < 0.005). These results suggest that MR abnormalities in the dentate nuclei may be evident consistently in patients with CTX. Proton MR spectroscopy data demonstrated widespread axonal damag e las shown by the decrease in N-acetylaspartate) and diffuse brain mitocho ndrial dysfunction las shown by the increase in brain parenchymal lactate) in patients with CTX. The close correlation seen between values of the puta tive axonal marker N-acetylaspartate and patients' disability scores sugges ts that proton MR spectroscopy can provide a useful measure of disease outc ome in CTX.