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Cerebrotendinous xanthomatosis (CTX) is a metabolic disease characterized by systemic signs and neurological impairment, which can be prevented if chenodeoxycholic acid (CDCA) treatment is started early. Despite brain MRI represents an essential diagnostic tool, the spectrum of findings is worth to be reappraised, and follow-up data are needed. We performed clinical evaluation and brain MRI in 38 CTX patients. Sixteen of them who were untreated at baseline examination underwent clinical and MRI follow-up after long-term treatment with CDCA. Brain MRI abnormalities included cortical and cerebellar atrophy, and T2W/FLAIR hyperintensity involving subcortical, periventricular, and cerebellar white matter, the brainstem and the dentate nuclei. Regarding the dentate nuclei, we also observed T1W/FLAIR hypointensity consistent with cerebellar vacuolation and T1W/FLAIR/SW hypointense alterations compatibly with calcification in a subgroup of patients. Long-term follow-up showed that clinical and neuroradiological stability or progression were almost invariably associated. In patients with cerebellar vacuolation at baseline, a worsening over time was observed, while subjects lacking vacuoles were clinically and neuroradiologically stable at follow-up. The brains of CTX patients very often show both supratentorial and infratentorial abnormalities at MRI, the latter being related to clinical disability and including a wide spectrum of dentate nuclei alterations. The presence of cerebellar vacuolation may be regarded as a useful biomarker of disease progression and unsatisfactory response to therapy. On the other hand, the absence of dentate nuclei signal alteration should be considered an indicator of better prognosis.

Cerebrotendinous xanthomatosis is an inherited autosomal recessive lipid storage disease caused by a 27-hydroxylase enzyme deficiency, characterised clinically by tendon xanthomas, premature cataracts, chronic diarrhoea and progressive neurologic dysfunction. The disease is very uncommon and there are very few pathological descriptions. We report a 52-year-old male who presented with a neuropsychiatric disorder and cognitive decline. Despite treatment the patient developed optic atrophy, parkinsonism and dementia and died. The autopsy revealed a nonspecific brain and cerebellar atrophy. Under microscopic examination, lipid crystal clefts, neuronal loss, demyelination, reactive astrocytosis and perivascular macrophages were found. These findings suggest the limited reversibility of the disease, and its poor prognosis, specially if treatment is not started early.