SPECT imaging for brain improvement quantification in a patient with cerebrotendinous xanthomatosis

Cerebrotendinous xanthomatosis is a rare recessive autosomal disease caused by mutations of the sterol 27-hydroxylase gene (CYP27), which leads to reduced synthesis of bile acids, particularly chenodeoxycholic acid (Cali et al, J Biol Chem. 1991;266:7779-7783; Gallus et al, Neurol Sci. 2006;27:143-149). The disease is characterized by progressive neurologic dysfunction due to accumulation of cholestanol in neurologic tissues (Moghadasian et al, Arch Neurol. 2002;59:527-529; Selva-O'Callaghan et al, Rheumatology. 2007;46:1212-1213). Long-term treatment with chenodeoxycholic acid can arrest or even reverse progression of the disease (Pierre et al, J Inherit Metab Dis. In press).Brain SPECT with 740 MBq of Tc-99m ethyl cysteinate dimmer, using a double-head gamma camera (Siemens E.cam) with high-resolution, low-energy parallel collimators was performed in our patient at onset and 2 years after starting chenodeoxycholic acid treatment. SPECT acquisitions were performed using a 360-degree orbit, 1 image/30 seg/3 degree, and 128 × 128 matrix. Reconstruction was by means of filtered back-projection, Butterworth 5/0.25, without attenuation correction. Pre- and post-SPECT dicom images were reoriented into Talairach space using NeuroGam (Segami Corporation). To visually identify abnormal perfusion regions, volume render brain image was computed, where abnormal perfusion regions were found by comparing with age-matched normal database, and Brodmann areas (BA) were quantified. Pre- versus post-treatment changes were computed by means of relative percentage between counts. Post-treatment SPECT showed better perfusion than pretreatment SPECT with an increase between 5% and 10% in frontal cortex (BA 9, BA 24, BA 32, BA 46, BA 47), parietal cortex (BA 5, BA 31), and temporal cortex (BA 20, BA 22, BA 28, BA 36, BA 37, BA 38), and with an increase of more than 10% in frontal cortex (BA 45) and parietal cortex (BA 23). This case illustrates the benefit of bile acid therapy for halting and even reversing neurologic retardation in this condition.