Leukodystrophy with a cerebellar cystic aspect and intracranial atherosclerosis: an atypical presentation of cerebrotendinous xanthomatosis.

Cerebrotendinous xanthomatosis (CTX, MIM #213700) is a rare autosomal recessive lipid storage disease where the clinical signs include juvenile cataracts, tendon xanthomas, intractable diarrhea, ataxia, and dementia. Diagnosis is based on increased levels of serum cholestanol and mitochondrial sterol 27-hydroxylase gene (CYP27) mutations. This report describes atypical MRI patterns in a late-onset patient. A 59-year-old woman, free of neurological symptoms up to the age of 50, including absence of mental retardation, presented with a 9-year history of progressive unsteadiness and cognitive impairment. Medical history consisted of a bilateral cataract surgically treated at the age of 47 and diarrhea with weight loss since her early 50s. Clinical examination revealed cerebellar ataxia, pyramidal, extrapyramidal (akinesia and rigidity) and pseudobulbar symptoms, dementia (Mini Mental Status 13/30) without tendon xanthomas. Brain CT scan showed spontaneous hyperdensity and increased diameter of the basilar artery (Fig. 1a). Brain MRI found hyperintensities on T2 and FLAIR sequences, involving middle cerebellar peduncles, pons, internal capsules, corpus callosum, and periventricular areas (Fig. 1b, c), without gadolinium-enhancement on T1 sequences. In addition, severe cerebellar atrophy and extensive hypointense signal of both cerebellar hemispheres were seen on T1 and FLAIR sequences (Fig. 1d–f). T2* sequences showed microbleeds in the cerebellar white matter and left thalamus (Fig. 1g). Extensive research of metabolic causes of leukodystrophy was negative, except for plasma 7 dehydrocholesterol (13.27 mol/l, normal \3 mol/l) and cholestanol levels (31.9 mol/l, normal \6.2 mol/l), which were increased.