Treatment with chenodeoxycholic acid in cerebrotendinous xanthomatosis: clinical, neurophysiological, and quantitative brain structural outcomes
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Cerebrotendinous xanthomatosis (CTX) is a rare neurodegenerative disease related to sterols metabolism. It affects both central and peripheral nervous systems but treatment with chenodeoxycholic acid (CDCA) has been reported to stabilize clinical scores and improve nerve conduction parameters. Few quantitative brain structural studies have been conducted to assess the effect of CDCA in CTX.
Methods and results
We collected retrospectively clinical, neurophysiological, and quantitative brain structural data in a cohort of 14 patients with CTX treated by CDCA over a mean period of 5 years. Plasma cholestanol levels normalized under treatment with CDCA within a few months. We observed a significant clinical improvement in patients up to 25 years old, whose treatment was initiated less than 15 years after the onset of neurological symptoms. Conversely, patients whose treatment was initiated more than 25 years after neurological disease onset continued their clinical deterioration. Eleven patients presented with a length-dependent peripheral neuropathy, whose electrophysiological parameters improved significantly under CDCA. Volumetric analyses in a subset of patients showed no overt volume loss under CDCA. Moreover, diffusion weighted imaging showed improved fiber integrity of the ponto-cerebellar and the internal capsule with CDCA. CDCA was well tolerated in all patients with CTX.
CDCA may reverse the pathophysiological process in patients with CTX, especially if treatment is initiated early in the disease process. Besides tendon xanthoma, this study stresses the need to consider plasma cholestanol measurement in any patient with infantile chronic diarrhea and/or jaundice, juvenile cataract, learning disability and/or autism spectrum disorder, pyramidal signs, cerebellar syndrome or peripheral neuropathy.
We are very grateful to the patients who participated in this study. We would also like to thank Damien Galanaud for MRI methods development, Isaac Adanyeguh for technical assistance, Philippe Couvert for molecular analyses, Frédéric Sedel and Yann Nadjar for patients referral. This study was supported the Investissements d’Avenir (Paris Institute of Neurosciences – IHU) grant number ANR-10-IAIHU-06.
Compliance with ethical standards
Conflict of interest
Maria del Mar Amador, Marion Masingue, Rabab Debs, Foudil Lamari, Vincent Perlbarg, Emmanuel Roze, Bertrand Degos declare that they have no conflict of interest.
Fanny Mochel has received an education grant from Sigma Tau pharmaceuticals.
This article does not contain any studies with animal subjects performed by the any of the authors.
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