Multiparametric in vivo analyses of the brain and spine identify structural and metabolic biomarkers in men with adrenomyeloneuropathy
Objective: Progressive myelopathy causes severe handicap in men with adrenomyeloneuropathy (AMN), an X-linked disorder due to ABCD1 pathogenic variants. At present, treatments are symptomatic but disease-modifying therapies are under evaluation. Given the small effect size of clinical scales in AMN,...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2021-01-01
|
| Series: | NeuroImage: Clinical |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213158221000103 |
| _version_ | 1818877699118071808 |
|---|---|
| author | Isaac M. Adanyeguh Xiaofang Lou Eavan McGovern Marie-Pierre Luton Magali Barbier Elise Yazbeck Romain Valabregue Dinesh Deelchand Pierre-Gilles Henry Fanny Mochel |
| author_facet | Isaac M. Adanyeguh Xiaofang Lou Eavan McGovern Marie-Pierre Luton Magali Barbier Elise Yazbeck Romain Valabregue Dinesh Deelchand Pierre-Gilles Henry Fanny Mochel |
| author_sort | Isaac M. Adanyeguh |
| collection | DOAJ |
| description | Objective: Progressive myelopathy causes severe handicap in men with adrenomyeloneuropathy (AMN), an X-linked disorder due to ABCD1 pathogenic variants. At present, treatments are symptomatic but disease-modifying therapies are under evaluation. Given the small effect size of clinical scales in AMN, biomarkers with higher effect size are needed. Here we used high-resolution magnetic resonance techniques to identify non-invasive in vivo biomarkers of the brain and spine with high effect sizes. Methods: We performed a multiparametric imaging and spectroscopy study in 23 male patients with AMN (age: 44 ± 11) and 23 male controls (age: 43 ± 11) of similar age and body-mass index. We combined (i) macrostructural analyses of the spine, using cross-sectional area (CSA) and magnetization transfer ratio (MTR), (ii) microstructural analyses of the spine and the brain, using diffusion tensor and the newly developed fixel-based analysis, and (iii) advanced metabolic analyses of the spine using metabolite cycling coupled to a semi-LASER sequences. Results: Macrostructural alterations (decrease in CSA and MTR) were observed in patients at all spinal cord levels studied (C1-T2 for CSA and C1-C5 for MTR) (p < 0.001). Microstructural alterations were observed in the spine and brain on diffusion tensor and fixel-based metrics though the latter showed higher effect sizes. Metabolic alterations were observed in patients as a decreased total N-acetylaspartate/myo-inositol ratio (p < 0.001). Overall, MTR showed the highest effect size. Conclusion: This cross-sectional study supports the use of multiparametric techniques that elucidate the structural, microstructural and metabolic alterations in AMN. These outcome measures should be tested longitudinally and in clinical trials. |
| first_indexed | 2024-12-19T14:02:26Z |
| format | Article |
| id | doaj.art-29c57df5b7a6468f866b5217ee81439f |
| institution | Directory Open Access Journal |
| issn | 2213-1582 |
| language | English |
| last_indexed | 2024-12-19T14:02:26Z |
| publishDate | 2021-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | NeuroImage: Clinical |
| spelling | doaj.art-29c57df5b7a6468f866b5217ee81439f2022-12-21T20:18:24ZengElsevierNeuroImage: Clinical2213-15822021-01-0129102566Multiparametric in vivo analyses of the brain and spine identify structural and metabolic biomarkers in men with adrenomyeloneuropathyIsaac M. Adanyeguh0Xiaofang Lou1Eavan McGovern2Marie-Pierre Luton3Magali Barbier4Elise Yazbeck5Romain Valabregue6Dinesh Deelchand7Pierre-Gilles Henry8Fanny Mochel9INSERM U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, F-75013 Paris, FranceINSERM U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, F-75013 Paris, FranceINSERM U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, F-75013 Paris, FranceINSERM U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, F-75013 Paris, FranceINSERM U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, F-75013 Paris, FranceINSERM U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, F-75013 Paris, FranceINSERM U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, F-75013 Paris, France; Center for NeuroImaging Research (CENIR), Institut du Cerveau et de la Moelle épinière, 75013 Paris, FranceCenter for Magnetic Resonance Research (CMRR), University of Minnesota, Minneapolis, MN, United StatesCenter for Magnetic Resonance Research (CMRR), University of Minnesota, Minneapolis, MN, United StatesINSERM U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, F-75013 Paris, France; AP-HP, Pitié-Salpêtrière University Hospital, Department of Genetics, Paris, France; University Pierre and Marie Curie, Neurometabolic Research Group, Paris, France; Corresponding author at: Reference Center for Neurometabolic Diseases, Department of Genetics, La Pitié-Salpêtrière University Hospital, 47 Boulevard de l’Hôpital, 75013 Paris, France.Objective: Progressive myelopathy causes severe handicap in men with adrenomyeloneuropathy (AMN), an X-linked disorder due to ABCD1 pathogenic variants. At present, treatments are symptomatic but disease-modifying therapies are under evaluation. Given the small effect size of clinical scales in AMN, biomarkers with higher effect size are needed. Here we used high-resolution magnetic resonance techniques to identify non-invasive in vivo biomarkers of the brain and spine with high effect sizes. Methods: We performed a multiparametric imaging and spectroscopy study in 23 male patients with AMN (age: 44 ± 11) and 23 male controls (age: 43 ± 11) of similar age and body-mass index. We combined (i) macrostructural analyses of the spine, using cross-sectional area (CSA) and magnetization transfer ratio (MTR), (ii) microstructural analyses of the spine and the brain, using diffusion tensor and the newly developed fixel-based analysis, and (iii) advanced metabolic analyses of the spine using metabolite cycling coupled to a semi-LASER sequences. Results: Macrostructural alterations (decrease in CSA and MTR) were observed in patients at all spinal cord levels studied (C1-T2 for CSA and C1-C5 for MTR) (p < 0.001). Microstructural alterations were observed in the spine and brain on diffusion tensor and fixel-based metrics though the latter showed higher effect sizes. Metabolic alterations were observed in patients as a decreased total N-acetylaspartate/myo-inositol ratio (p < 0.001). Overall, MTR showed the highest effect size. Conclusion: This cross-sectional study supports the use of multiparametric techniques that elucidate the structural, microstructural and metabolic alterations in AMN. These outcome measures should be tested longitudinally and in clinical trials.http://www.sciencedirect.com/science/article/pii/S2213158221000103AdrenomyeloneuropathySpinal cord imagingMetabolite cyclingFixel-based analysisImaging biomarkersSpinal cord toolbox |
| spellingShingle | Isaac M. Adanyeguh Xiaofang Lou Eavan McGovern Marie-Pierre Luton Magali Barbier Elise Yazbeck Romain Valabregue Dinesh Deelchand Pierre-Gilles Henry Fanny Mochel Multiparametric in vivo analyses of the brain and spine identify structural and metabolic biomarkers in men with adrenomyeloneuropathy NeuroImage: Clinical Adrenomyeloneuropathy Spinal cord imaging Metabolite cycling Fixel-based analysis Imaging biomarkers Spinal cord toolbox |
| title | Multiparametric in vivo analyses of the brain and spine identify structural and metabolic biomarkers in men with adrenomyeloneuropathy |
| title_full | Multiparametric in vivo analyses of the brain and spine identify structural and metabolic biomarkers in men with adrenomyeloneuropathy |
| title_fullStr | Multiparametric in vivo analyses of the brain and spine identify structural and metabolic biomarkers in men with adrenomyeloneuropathy |
| title_full_unstemmed | Multiparametric in vivo analyses of the brain and spine identify structural and metabolic biomarkers in men with adrenomyeloneuropathy |
| title_short | Multiparametric in vivo analyses of the brain and spine identify structural and metabolic biomarkers in men with adrenomyeloneuropathy |
| title_sort | multiparametric in vivo analyses of the brain and spine identify structural and metabolic biomarkers in men with adrenomyeloneuropathy |
| topic | Adrenomyeloneuropathy Spinal cord imaging Metabolite cycling Fixel-based analysis Imaging biomarkers Spinal cord toolbox |
| url | http://www.sciencedirect.com/science/article/pii/S2213158221000103 |
| work_keys_str_mv | AT isaacmadanyeguh multiparametricinvivoanalysesofthebrainandspineidentifystructuralandmetabolicbiomarkersinmenwithadrenomyeloneuropathy AT xiaofanglou multiparametricinvivoanalysesofthebrainandspineidentifystructuralandmetabolicbiomarkersinmenwithadrenomyeloneuropathy AT eavanmcgovern multiparametricinvivoanalysesofthebrainandspineidentifystructuralandmetabolicbiomarkersinmenwithadrenomyeloneuropathy AT mariepierreluton multiparametricinvivoanalysesofthebrainandspineidentifystructuralandmetabolicbiomarkersinmenwithadrenomyeloneuropathy AT magalibarbier multiparametricinvivoanalysesofthebrainandspineidentifystructuralandmetabolicbiomarkersinmenwithadrenomyeloneuropathy AT eliseyazbeck multiparametricinvivoanalysesofthebrainandspineidentifystructuralandmetabolicbiomarkersinmenwithadrenomyeloneuropathy AT romainvalabregue multiparametricinvivoanalysesofthebrainandspineidentifystructuralandmetabolicbiomarkersinmenwithadrenomyeloneuropathy AT dineshdeelchand multiparametricinvivoanalysesofthebrainandspineidentifystructuralandmetabolicbiomarkersinmenwithadrenomyeloneuropathy AT pierregilleshenry multiparametricinvivoanalysesofthebrainandspineidentifystructuralandmetabolicbiomarkersinmenwithadrenomyeloneuropathy AT fannymochel multiparametricinvivoanalysesofthebrainandspineidentifystructuralandmetabolicbiomarkersinmenwithadrenomyeloneuropathy |