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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/21638

Title: Normalisation of brain spectroscopy findings in Niemann-Pick disease type C patients treated with miglustat
Authors: Sedel, Frédéric
Chabrol, Brigitte
Audoin, Bertrand
Kaphan, Elsa
Tranchant, Christine
Burzykowski, Tomasz
Tourbah, Ayman
Vanier, Marie T.
Galanaud, Damien
Issue Date: 2016
Citation: JOURNAL OF NEUROLOGY, 263 (5), p. 927-936
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.
Notes: [Sedel, Frederic] Salpetriere Hosp, AP HP, Dept Neurol, Federat Nervous Syst Dis, 47 Blvd Hop, F-75651 Paris 13, France. [Sedel, Frederic] Univ Paris 06, Neurometab Unit & Reference Ctr Lysosomal Dis, GRC13UPMC, Salpetriere Hosp,AP HP, Paris, France. [Chabrol, Brigitte] CHU Marseille, La Timone Hosp, Dept Pediat, Marseille, France. [Audoin, Bertrand] Aix Marseille Univ, Dept Neurol, CNRS, Div Clin Neurosci,CRMBM UMR 7339,Timone Hosp,AP H, Marseille, France. [Kaphan, Elsa] CHU Timone, Dept Neurol, Div Clin Neurosci, AP HM, Marseille, France. [Tranchant, Christine] CHU Hautepierre, Dept Neurol, Strasbourg, France. [Tranchant, Christine] FMTS, Strasbourg, France. [Burzykowski, Tomasz] Int Inst Drug Dev, Louvain, Belgium. [Burzykowski, Tomasz] Hasselt Univ, Hasselt, Belgium. [Tourbah, Ayman] Univ Paris 08, Dept Neurol, Cent Univ Hosp, Fac Med Reims URCA, St Denis, France. [Tourbah, Ayman] Univ Paris 08, EA 2027, St Denis, France. [Vanier, Marie T.] INSERM, U820, F-69008 Lyon, France. [Galanaud, Damien] Univ Paris 06, Dept Neuroradiol, Paris, France.
URI: http://hdl.handle.net/1942/21638
DOI: 10.1007/s00415-016-8051-1
ISI #: 000376141000011
ISSN: 0340-5354
Category: A1
Type: Journal Contribution
Validation: ecoom, 2017
Appears in Collections: Research publications

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