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@ARTICLE{Catarino:139788,
author = {Catarino, Claudia B and Vollmar, Christian and Küpper,
Clemens and Seelos, Klaus and Gallenmüller, Constanze and
Bartkiewicz, Joanna and Biskup, Saskia and Hörtnagel,
Konstanze and Klopstock, Thomas},
title = {{B}rain diffusion tensor imaging changes in
cerebrotendinous xanthomatosis reversed with treatment.},
journal = {Journal of neurology},
volume = {265},
number = {2},
issn = {0340-5354},
address = {Berlin},
publisher = {Springer73057},
reportid = {DZNE-2020-06110},
pages = {388-393},
year = {2018},
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 = {Adult / Anisotropy / Brain: diagnostic imaging / Brain:
drug effects / Chenodeoxycholic Acid: pharmacology /
Chenodeoxycholic Acid: therapeutic use / Cholestanetriol
26-Monooxygenase: genetics / Diffusion Tensor Imaging /
Female / Gastrointestinal Agents: pharmacology /
Gastrointestinal Agents: therapeutic use / Humans / Image
Processing, Computer-Assisted / Magnetic Resonance Imaging /
Male / Mutation: genetics / Prospective Studies /
Xanthomatosis, Cerebrotendinous: diagnostic imaging /
Xanthomatosis, Cerebrotendinous: drug therapy /
Xanthomatosis, Cerebrotendinous: genetics / Gastrointestinal
Agents (NLM Chemicals) / Chenodeoxycholic Acid (NLM
Chemicals) / CYP27A1 protein, human (NLM Chemicals) /
Cholestanetriol 26-Monooxygenase (NLM Chemicals)},
cin = {Ext LMU Klinik / AG Levin},
ddc = {610},
cid = {I:(DE-2719)5000049 / I:(DE-2719)1111016},
pnm = {344 - Clinical and Health Care Research (POF3-344)},
pid = {G:(DE-HGF)POF3-344},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:29260356},
doi = {10.1007/s00415-017-8711-9},
url = {https://pub.dzne.de/record/139788},
}