16.03.2016 | Original Communication | Ausgabe 5/2016 Open Access

Normalisation of brain spectroscopy findings in Niemann–Pick disease type C patients treated with miglustat

Zeitschrift:: Journal of Neurology > Ausgabe 5/2016

Autoren:: Frédéric Sedel, Brigitte Chabrol, Bertrand Audoin, Elsa Kaphan, Christine Tranchant, Tomasz Burzykowski, Ayman Tourbah, Marie T. Vanier, Damien Galanaud

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The online version of this article (doi:10.1007/s00415-016-8051-1) contains supplementary material, which is available to authorized users.

Abstract

Niemann–Pick disease type C (NP-C) is a fatal progressive neurolipidosis involving neuronal storage of cholesterol and gangliosides. Miglustat, an inhibitor of glycosphingolipid synthesis, has been approved to treat neurological manifestations in adults and children with NP-C. This open-label observational study in adults with confirmed NP-C evaluated the efficacy of miglustat (200 mg t.i.d.) based on composite functional disability (CFD) scores and brain proton magnetic resonance spectroscopy (H-MRS) measurement of choline (Cho)/N-acetyl aspartate (NAA) ratio in the centrum ovale. Overall, 16 patients were included and received miglustat for a mean period of 30.6 months: 12 continued on miglustat throughout follow up, and 4 discontinued miglustat because of adverse effects (n = 2) or perceived lack of efficacy (n = 2). In the ‘continued’ subgroup, the mean (SD) annual progression of CFD scores decreased from 0.75 (0.94) before treatment to 0.29 (1.29) during the period between miglustat initiation and last follow-up. In the discontinued subgroup, CFD progression increased from 0.48 (0.44) pre-treatment to 1.49 (1.31) at last follow up (off treatment). Mean (SD) Cho/NAA ratio [normal level 0.48 (0.076)] decreased during miglustat treatment in the continued subgroup: 0.64 (0.12) at baseline (miglustat initiation), 0.59 (0.17) at 12-month follow up, and 0.48 (0.09) at 24-month follow up. Cho/NAA ratio remained relatively stable in the discontinued subgroup: 0.57 (0.15), 0.53 (0.04) and 0.55 (0.09), respectively. In conclusion, H-MRS Cho/NAA ratio might serve as an objective, quantitative neurological marker of brain dysfunction in NP-C, allowing longitudinal analysis of the therapeutic effect of miglustat.

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Supplementary material 1 (DOCX 30 kb)

415_2016_8051_MOESM1_ESM.docx

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Titel: Normalisation of brain spectroscopy findings in Niemann–Pick disease type C patients treated with miglustat
Autoren:: Frédéric Sedel
Brigitte Chabrol
Bertrand Audoin
Elsa Kaphan
Christine Tranchant
Tomasz Burzykowski
Ayman Tourbah
Marie T. Vanier
Damien Galanaud
Publikationsdatum: 16.03.2016
DOI: https://doi.org/10.1007/s00415-016-8051-1
Verlag: Springer Berlin Heidelberg
Zeitschrift: Journal of Neurology
Ausgabe 5/2016
Print ISSN: 0340-5354
Elektronische ISSN: 1432-1459

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Normalisation of brain spectroscopy findings in Niemann–Pick disease type C patients treated with miglustat

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Abstract

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