Evolution of structural neuroimaging biomarkers in a series of adult patients with Niemann-Pick type C under treatment
Identifieur interne : 000036 ( Main/Exploration ); précédent : 000035; suivant : 000037Evolution of structural neuroimaging biomarkers in a series of adult patients with Niemann-Pick type C under treatment
Auteurs : Marion Masingue [France] ; Isaac Adanyeguh [France] ; Yann Nadjar [France] ; Frédéric Sedel [France] ; Damien Galanaud [France] ; Fanny Mochel [France]Source :
- Orphanet Journal of Rare Diseases [ 1750-1172 ] ; 2017.
Abstract
Niemann-Pick type C (NPC) disease is a lysosomal storage disorder characterized by a wide clinical spectrum and non-specific conventional magnetic resonance imaging (MRI) signs. As substrate reduction therapy with miglustat is now used in almost all patients, its efficacy and the course of the disease are sometimes difficult to evaluate. Neuroimaging biomarkers could prove useful in this matter. We first performed a retrospective analysis of volumetric and diffusion tensor imaging (DTI) data on 13 adult NPC patients compared to 13 controls of similar age and sex. Eleven NPC patients were then studied using the same neuroimaging modalities over a mean of 5 years. The NPC composite score was used to evaluate disease severity.
NPC patients showed atrophy in basal ganglia – pallidum (
This is the first study conducted on a series of adult NPC patients using two neuroimaging modalities and followed under treatment. It confirmed that NPC patients displayed cerebral atrophy in several regions of interest compared to controls. Furthermore, miglustat showed an early effect on diffusion metrics in treated patients. DTI can detect brain microstructure alterations caused by neurometabolic dysfunction. Its potential as a biomarker in NPC shall be further evaluated in upcoming therapeutic trials.
The online version of this article (doi:10.1186/s13023-017-0579-3) contains supplementary material, which is available to authorized users.
Url:
DOI: 10.1186/s13023-017-0579-3
PubMed: 28148276
PubMed Central: 5289046
Affiliations:
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first="Damien" last="Galanaud">Damien Galanaud</name><affiliation wicri:level="3"><nlm:aff id="Aff1">Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC University Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC University Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2150 9058</institution-id><institution-id institution-id-type="GRID">grid.411439.a</institution-id><institution>Department of Neuroradiology, AP-HP,</institution><institution>Pitié-Salpêtrière University 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institution-id-type="ISNI">0000 0001 2150 9058</institution-id><institution-id institution-id-type="GRID">grid.411439.a</institution-id><institution>Department of Genetics, AP-HP,</institution><institution>Pitié-Salpêtrière University Hospital,</institution></institution-wrap>Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Paris</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff7"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 1955 3500</institution-id><institution-id institution-id-type="GRID">grid.5805.8</institution-id><institution></institution><institution>University Pierre and Marie Curie, Neurometabolic Research Group,</institution></institution-wrap>Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Paris</wicri:regionArea></affiliation></author></analytic><series><title level="j">Orphanet Journal of Rare Diseases</title><idno type="eISSN">1750-1172</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>Niemann-Pick type C (NPC) disease is a lysosomal storage disorder characterized by a wide clinical spectrum and non-specific conventional magnetic resonance imaging (MRI) signs. As substrate reduction therapy with miglustat is now used in almost all patients, its efficacy and the course of the disease are sometimes difficult to evaluate. Neuroimaging biomarkers could prove useful in this matter. We first performed a retrospective analysis of volumetric and diffusion tensor imaging (DTI) data on 13 adult NPC patients compared to 13 controls of similar age and sex. Eleven NPC patients were then studied using the same neuroimaging modalities over a mean of 5 years. The NPC composite score was used to evaluate disease severity.</p></sec><sec><title>Results</title><p>NPC patients showed atrophy in basal ganglia – pallidum (<italic>p</italic> = 0.029), caudate nucleus (<italic>p</italic> = 0.022), putamen (<italic>p</italic> = 0.002) and thalamus (<italic>p</italic> < 0.001) – cerebral peduncles (<italic>p</italic> = 0.003) and corpus callosum (<italic>p</italic> = 0.006), compared to controls. NPC patients also displayed decreased fractional anisotropy (FA) in several regions of interest – corona radiata (<italic>p</italic> = 0.015), internal capsule (<italic>p</italic> = 0.007), corpus callosum (<italic>p</italic> = 0.032) and cingulate gyrus (<italic>p</italic> = 0.002) – as well as a broad increase in radial diffusivity (<italic>p</italic> < 0.001), compared to controls. Over time, 3 patients worsened clinically, including 2 patients who interrupted treatment, while 8 patients remained stable. With miglustat, no significant volumetric change was observed but FA improved after 2 years in the corpus callosum and the corona radiata of NPC patients (<italic>n</italic> = 4; <italic>p</italic> = 0.029) – although that was no longer observed at further time points.</p></sec><sec><title>Conclusion</title><p>This is the first study conducted on a series of adult NPC patients using two neuroimaging modalities and followed under treatment. It confirmed that NPC patients displayed cerebral atrophy in several regions of interest compared to controls. Furthermore, miglustat showed an early effect on diffusion metrics in treated patients. DTI can detect brain microstructure alterations caused by neurometabolic dysfunction. Its potential as a biomarker in NPC shall be further evaluated in upcoming therapeutic trials.</p></sec><sec><title>Electronic supplementary material</title><p>The online version of this article (doi:10.1186/s13023-017-0579-3) contains supplementary material, which is available to authorized users.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Nixon, Ra" uniqKey="Nixon R">RA Nixon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Adanyeguh, Im" uniqKey="Adanyeguh I">IM Adanyeguh</name></author><author><name sortKey="Rinaldi, D" uniqKey="Rinaldi D">D Rinaldi</name></author><author><name sortKey="Henry, Pg" uniqKey="Henry P">PG Henry</name></author><author><name sortKey="Caillet, S" uniqKey="Caillet S">S Caillet</name></author><author><name sortKey="Valabregue, R" uniqKey="Valabregue R">R Valabregue</name></author><author><name sortKey="Durr, A" uniqKey="Durr A">A 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B" uniqKey="Audoin B">B Audoin</name></author><author><name sortKey="Kaphan, E" uniqKey="Kaphan E">E Kaphan</name></author><author><name sortKey="Tranchant, C" uniqKey="Tranchant C">C Tranchant</name></author><author><name sortKey="Burzykowski, T" uniqKey="Burzykowski T">T Burzykowski</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Millat, G" uniqKey="Millat G">G Millat</name></author><author><name sortKey="Bailo, N" uniqKey="Bailo N">N Baïlo</name></author><author><name sortKey="Molinero, S" uniqKey="Molinero S">S Molinero</name></author><author><name sortKey="Rodriguez, C" uniqKey="Rodriguez C">C Rodriguez</name></author><author><name sortKey="Chikh, K" uniqKey="Chikh K">K Chikh</name></author><author><name sortKey="Vanier, Mt" uniqKey="Vanier M">MT Vanier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pineda, M" uniqKey="Pineda M">M Pineda</name></author><author><name sortKey="Perez Poyato, Ms" uniqKey="Perez 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Group</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Der Eerden, Aw" uniqKey="Van Der Eerden A">AW Van der Eerden</name></author><author><name sortKey="Khalilzadeh, O" uniqKey="Khalilzadeh O">O Khalilzadeh</name></author><author><name sortKey="Perbarg, V" uniqKey="Perbarg V">V Perbarg</name></author><author><name sortKey="Dinkel, J" uniqKey="Dinkel J">J Dinkel</name></author><author><name sortKey="Sanchez, P" uniqKey="Sanchez P">P Sanchez</name></author><author><name sortKey="Vos, Pe" uniqKey="Vos P">PE Vos</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Basso, M" uniqKey="Basso M">M Basso</name></author><author><name sortKey="Yang, J" uniqKey="Yang J">J Yang</name></author><author><name sortKey="Warren, L" uniqKey="Warren L">L Warren</name></author><author><name sortKey="Macavoy, Mg" uniqKey="Macavoy M">MG MacAvoy</name></author><author><name sortKey="Varma, P" uniqKey="Varma P">P Varma</name></author><author><name sortKey="Bronen, Ra" uniqKey="Bronen R">RA Bronen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Trouard, Tp" uniqKey="Trouard T">TP Trouard</name></author><author><name sortKey="Heidenreich, Ra" uniqKey="Heidenreich R">RA Heidenreich</name></author><author><name sortKey="Seeger, Jf" uniqKey="Seeger J">JF Seeger</name></author><author><name sortKey="Erickson, Rp" uniqKey="Erickson R">RP Erickson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Davies Thompson, J" uniqKey="Davies Thompson J">J Davies-Thompson</name></author><author><name sortKey="Vasavur, I" uniqKey="Vasavur I">I Vasavur</name></author><author><name sortKey="Scheel, M" uniqKey="Scheel M">M Scheel</name></author><author><name sortKey="Rauscher, A" uniqKey="Rauscher A">A Rauscher</name></author><author><name sortKey="Barton, Jjs" uniqKey="Barton J">JJS Barton</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>France</li></country><region><li>Île-de-France</li></region><settlement><li>Paris</li></settlement></list><tree><country name="France"><region name="Île-de-France"><name sortKey="Masingue, Marion" sort="Masingue, Marion" uniqKey="Masingue M" first="Marion" last="Masingue">Marion Masingue</name></region><name sortKey="Adanyeguh, Isaac" sort="Adanyeguh, Isaac" uniqKey="Adanyeguh I" first="Isaac" last="Adanyeguh">Isaac Adanyeguh</name><name sortKey="Galanaud, Damien" sort="Galanaud, Damien" uniqKey="Galanaud D" first="Damien" last="Galanaud">Damien Galanaud</name><name sortKey="Galanaud, Damien" sort="Galanaud, Damien" uniqKey="Galanaud D" first="Damien" last="Galanaud">Damien Galanaud</name><name sortKey="Masingue, Marion" sort="Masingue, Marion" uniqKey="Masingue M" first="Marion" last="Masingue">Marion Masingue</name><name sortKey="Mochel, Fanny" sort="Mochel, Fanny" uniqKey="Mochel F" first="Fanny" last="Mochel">Fanny Mochel</name><name sortKey="Mochel, Fanny" sort="Mochel, Fanny" uniqKey="Mochel F" first="Fanny" last="Mochel">Fanny Mochel</name><name sortKey="Mochel, Fanny" sort="Mochel, Fanny" uniqKey="Mochel F" first="Fanny" last="Mochel">Fanny Mochel</name><name sortKey="Nadjar, Yann" sort="Nadjar, Yann" uniqKey="Nadjar Y" first="Yann" last="Nadjar">Yann Nadjar</name><name sortKey="Nadjar, Yann" sort="Nadjar, Yann" uniqKey="Nadjar Y" first="Yann" last="Nadjar">Yann Nadjar</name><name sortKey="Sedel, Frederic" sort="Sedel, Frederic" uniqKey="Sedel F" first="Frédéric" last="Sedel">Frédéric Sedel</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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