The spectrum of magnetic resonance findings in cerebrotendinous xanthomatosis: redefinition and evidence of new markers of disease progression.
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.
Unit of Neurology and Neurometabolic Disorders, Department of Medicine, Surgery and Neurosciences, University of Siena, Viale Bracci 2, 53100, Siena, Italy.
Andrea
A
Mignarri
Unit of Neurology and Neurometabolic Disorders, Department of Medicine, Surgery and Neurosciences, University of Siena, Viale Bracci 2, 53100, Siena, Italy. dotti@unisi.it.
Maria Teresa
MT
Dotti
Unit of Neurology and Neurometabolic Disorders, Department of Medicine, Surgery and Neurosciences, University of Siena, Viale Bracci 2, 53100, Siena, Italy.
Antonio
A
Federico
Unit of Neurology and Neurometabolic Disorders, Department of Medicine, Surgery and Neurosciences, University of Siena, Viale Bracci 2, 53100, Siena, Italy.
Nicola
N
De Stefano
Unit of Neurology and Neurometabolic Disorders, Department of Medicine, Surgery and Neurosciences, University of Siena, Viale Bracci 2, 53100, Siena, Italy.
Marco
M
Battaglini
Unit of Diagnostic and Therapeutic Neuroradiology, Azienda Ospedaliera Siena, Siena, Italy.
Irene
I
Grazzini
Unit of Diagnostic and Therapeutic Neuroradiology, Azienda Ospedaliera Siena, Siena, Italy.
Paolo
P
Galluzzi
Unit of Diagnostic and Therapeutic Neuroradiology, Azienda Ospedaliera Siena, Siena, Italy.
Lucia
L
Monti
D000293:Adolescent; D000328:Adult; D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D019294:Xanthomatosis, Cerebrotendinous / Q000000981:diagnostic imaging* / Q000473:pathology / Q000503:physiopathology*; D055815:Young Adult
Cerebellar vacuolation; Cerebrotendinous xanthomatosis; Chenodeoxycholic acid; Dentate nuclei; MRI