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Journal of Neurology

, Volume 265, Issue 2, pp 388–393 | Cite as

Brain diffusion tensor imaging changes in cerebrotendinous xanthomatosis reversed with treatment

  • Claudia B. Catarino
  • Christian Vollmar
  • Clemens Küpper
  • Klaus Seelos
  • Constanze Gallenmüller
  • Joanna Bartkiewicz
  • Saskia Biskup
  • Konstanze Hörtnagel
  • Thomas KlopstockEmail author
Original Communication

Abstract

Cerebrotendinous xanthomatosis (CTX, MIM 213700) is a rare autosomal recessive lipid storage disorder caused by CYP27A1 mutations. Treatment with chenodeoxycholic acid (CDCA) may slow the progression of the disease and reverse some symptoms in a proportion of patients. In a non-consanguineous Caucasian family, two siblings with CTX were evaluated before treatment and prospectively followed-up every 6 months after starting CDCA therapy, using systematic clinical examination, neuropsychological tests, laboratory tests, electroencephalography (EEG) and brain MRI, diffusion tensor imaging (DTI) and tractography. A 30-year-old patient and her 27-year-old brother were referred for progressive spastic paraparesis. Both had epilepsy, learning difficulties, chronic diarrhoea and juvenile-onset cataracts. CTX was diagnosed by increased cholestanol levels and compound heterozygosity for CYP27A1 mutations. Therapy with CDCA led to resolution of chronic diarrhoea, normalisation of serum cholestanol and EEG, and a progressive improvement in gait, cognition and seizure control. Before treatment, conventional brain MRI showed no CTX-related abnormalities for the proband and no cerebellar abnormalities for the brother, while DTI showed reduced fractional anisotropy (FA) and tract-density in the cerebellum and widespread cerebral reductions of FA in both patients, compared to a group of 35 healthy controls. Repeated DTI after starting therapy showed progressive increases of cerebellar tract density and of cerebral FA. In patients with CTX, therapy with CDCA may lead to significant clinical improvement, with normalisation of biochemical and electrophysiological biomarkers. DTI and tractography may detect changes when the conventional MRI is unremarkable and may provide potential neuroimaging biomarkers for monitoring treatment response in CTX, while the conventional MRI remains unchanged.

Keywords

Cerebrotendinous xanthomatosis Chenodeoxycholic acid DTI Tractography Spastic paraplegia 

Notes

Acknowledgements

We are grateful to the patients and their relatives.

Funding

We declare no funding.

Compliance with ethical standards

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical standard

This study has been approved by the appropriate ethics committee and has, therefore, been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki.

Supplementary material

415_2017_8711_MOESM1_ESM.pdf (344 kb)
Supplementary material 1 (PDF 344 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Department of Neurology with Friedrich-Baur InstituteUniversity Hospital of the Ludwig-Maximilians-Universität MünchenMunichGermany
  2. 2.Department of NeuroradiologyUniversity Hospital of the Ludwig-Maximilians-Universität MünchenMunichGermany
  3. 3.German Center for Neurodegenerative Diseases (DZNE)MunichGermany
  4. 4.CeGaT GmbH und Praxis für HumangenetikTübingenGermany
  5. 5.Munich Cluster for Systems Neurology (SyNergy)MunichGermany

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