The spectrum of magnetic resonance findings in cerebrotendinous xanthomatosis: redefinition and evidence of new markers of disease progression

• DOI: 10.1007/s00415-017-8440-0
• Publication Date: 2017-03-21T08:11:44Z
• Authors: Andrea Mignarri; Maria Teresa Dotti; Antonio Federico; Nicola De Stefano; Marco Battaglini; Irene Grazzini; Paolo Galluzzi; Lucia Monti
• Keywords: Adult; Male; Adolescent; Severity of Illness Index; Young Adult; 03 medical and health sciences; 0302 clinical medicine; Image Processing, Computer-Assisted; Humans; Cerebellar vacuolation; Aged; Cerebellar vacuolation; Cerebrotendinous xanthomatosis; Chenodeoxycholic acid; Dentate nuclei; MRI; Neurology; Neurology (clinical); Brain; Xanthomatosis, Cerebrotendinous; Middle Aged; Magnetic Resonance Imaging; Neurology; Cerebrotendinous xanthomatosi; Disease Progression; Dentate nuclei; Female; Neurology (clinical); Chenodeoxycholic acid; MRI; Follow-Up Studies

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.