What is the role of imaging studies in the workup of cerebrotendinous xanthomatosis (CTX)?

Updated: Jun 20, 2019
  • Author: Robert D Steiner, MD; Chief Editor: Maria Descartes, MD  more...
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The brains of individuals with cerebrotendinous xanthomatosis often show both supratentorial and infratentorial abnormalities on MRI. The findings on MRI and CT scanning include cortical and cerebellar atrophy of the brain, as well as focal lesions (including demyelinating lesions and, rarely, xanthomata) in the cerebellum, basal ganglia, and cerebrum. Typical patterns on brain MRI include bilateral lesions consistent with a metabolic abnormality. T2/FLAIR hyperintensity of the subcortical, periventricular, cerebellar white matter, brainstem, and dentate nuclei are characteristic of cerebrotendinous xanthomatosis. [63, 64] T2 abnormalities are also found in the globus pallidus, substantia nigra, and inferior olives with extension into the surrounding white matter in later years of the disease. Some hypointensity in the dentate nuclei was related to hemosiderin and calcification and was found on autopsy. Cerebrotendinous xanthomatosis should be considered in the differential diagnosis of leukodystrophies. [65]

A reasonably large 2017 study showed T1/FLAIR hypointensity consistent with cerebellar vacuolation and T1/FLAIR/SW hypointense alterations compatible with calcification in a subgroup of patients with cerebrotendinous xanthomatosis. Long-term follow-up showed that clinical and neuroradiological stability or progression were almost invariably associated. In patients with cerebellar vacuolation at baseline, worsening over time was observed, while patients lacking vacuoles were clinically and neuroradiologically stable at follow-up. Infratentorial abnormalities on MRI are related to clinical disability. The presence of cerebellar vacuolation may be regarded as a useful biomarker of disease progression and unsatisfactory response to therapy. Conversely, the absence of dentate nuclei signal alteration should be considered an indicator of better prognosis. [64]

Brain MRI fluid attenuation inversion recovery (FLAIR) sequences in one patient revealed cortical and subcortical hyperintensities in the temporal lobes) and globus pallidus. T2-weighted MRI revealed cerebellar hyperintensities within the dentate nucleus. Hypointensities were seen on T1-weighted and susceptibility MRI scans within the cerebellum at the level of the midbrain. [63]

Magnetic resonance spectroscopy reveals diffuse mitochondrial dysfunction and axonal damage, with large amounts of lactate and decreased N -acetylaspartate in the periventricular white matter and cerebellar hemispheres. [63]

Diffusion tensor imaging (DTI) may show abnormalities despite normal conventional brain MRI findings. DTI showed reduced fractional anisotropy (FA) and tract-density in the cerebellum and widespread cerebral reductions of FA. DTI after therapy initiation showed progressive increases in cerebellar tract density and cerebral FA. [66]

Isolated spinal cord white matter disease has been described. [67, 68] MRI may reveal increased intensity in the lateral and dorsal columns, even in mainly cerebral forms of the disease. [63] Magnetization transfer imaging has been found to be a reliable quantitative indicator of the extent of damage in the brain parenchyma. [68] MRI can also be used to evaluate possible tendon xanthomata outside the central nervous system; enlargement of the tendons is evident in such cases.


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