A Postmortem MRI Study of Cerebrovascular Disease and Iron Content at End-Stage of Fragile X-Associated Tremor/Ataxia Syndrome
Brain changes at the end-stage of fragile X-associated tremor/ataxia syndrome (FXTAS) are largely unknown due to mobility impairment. We conducted a postmortem MRI study of FXTAS to quantify cerebrovascular disease, brain atrophy and iron content, and examined their relationships using principal com...
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MDPI AG
2023-07-01
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| Online Access: | https://www.mdpi.com/2073-4409/12/14/1898 |
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| author | Jun Yi Wang Gerard J. Sonico Maria Jimena Salcedo-Arellano Randi J. Hagerman Veronica Martinez-Cerdeno |
| author_facet | Jun Yi Wang Gerard J. Sonico Maria Jimena Salcedo-Arellano Randi J. Hagerman Veronica Martinez-Cerdeno |
| author_sort | Jun Yi Wang |
| collection | DOAJ |
| description | Brain changes at the end-stage of fragile X-associated tremor/ataxia syndrome (FXTAS) are largely unknown due to mobility impairment. We conducted a postmortem MRI study of FXTAS to quantify cerebrovascular disease, brain atrophy and iron content, and examined their relationships using principal component analysis (PCA). Intracranial hemorrhage (ICH) was observed in 4/17 FXTAS cases, among which one was confirmed by histologic staining. Compared with seven control brains, FXTAS cases showed higher ratings of T2-hyperintensities (indicating cerebral small vessel disease) in the cerebellum, globus pallidus and frontoparietal white matter, and significant atrophy in the cerebellar white matter, red nucleus and dentate nucleus. PCA of FXTAS cases revealed negative associations of T2-hyperintensity ratings with anatomic volumes and iron content in the white matter, hippocampus and amygdala, that were independent from a highly correlated number of regions with ICH and iron content in subcortical nuclei. Post-hoc analysis confirmed PCA findings and further revealed increased iron content in the white matter, hippocampus and amygdala in FXTAS cases compared to controls, after adjusting for T2-hyperintensity ratings. These findings indicate that both ischemic and hemorrhagic brain damage may occur in FXTAS, with the former being marked by demyelination/iron depletion and atrophy, and the latter by ICH and iron accumulation in basal ganglia. |
| first_indexed | 2024-03-11T01:12:08Z |
| format | Article |
| id | doaj.art-e08e59afce094c16874f9ab6c28665bf |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T01:12:08Z |
| publishDate | 2023-07-01 |
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| series | Cells |
| spelling | doaj.art-e08e59afce094c16874f9ab6c28665bf2023-11-18T18:46:45ZengMDPI AGCells2073-44092023-07-011214189810.3390/cells12141898A Postmortem MRI Study of Cerebrovascular Disease and Iron Content at End-Stage of Fragile X-Associated Tremor/Ataxia SyndromeJun Yi Wang0Gerard J. Sonico1Maria Jimena Salcedo-Arellano2Randi J. Hagerman3Veronica Martinez-Cerdeno4Center for Mind and Brain, University of California Davis, Davis, CA 95618, USAImaging Research Center, University of California Davis, Sacramento, CA 95817, USADepartment of Pathology and Laboratory Medicine, University of California Davis School of Medicine, Sacramento, CA 95817, USAMIND Institute, University of California Davis Health, Sacramento, CA 95817, USADepartment of Pathology and Laboratory Medicine, University of California Davis School of Medicine, Sacramento, CA 95817, USABrain changes at the end-stage of fragile X-associated tremor/ataxia syndrome (FXTAS) are largely unknown due to mobility impairment. We conducted a postmortem MRI study of FXTAS to quantify cerebrovascular disease, brain atrophy and iron content, and examined their relationships using principal component analysis (PCA). Intracranial hemorrhage (ICH) was observed in 4/17 FXTAS cases, among which one was confirmed by histologic staining. Compared with seven control brains, FXTAS cases showed higher ratings of T2-hyperintensities (indicating cerebral small vessel disease) in the cerebellum, globus pallidus and frontoparietal white matter, and significant atrophy in the cerebellar white matter, red nucleus and dentate nucleus. PCA of FXTAS cases revealed negative associations of T2-hyperintensity ratings with anatomic volumes and iron content in the white matter, hippocampus and amygdala, that were independent from a highly correlated number of regions with ICH and iron content in subcortical nuclei. Post-hoc analysis confirmed PCA findings and further revealed increased iron content in the white matter, hippocampus and amygdala in FXTAS cases compared to controls, after adjusting for T2-hyperintensity ratings. These findings indicate that both ischemic and hemorrhagic brain damage may occur in FXTAS, with the former being marked by demyelination/iron depletion and atrophy, and the latter by ICH and iron accumulation in basal ganglia.https://www.mdpi.com/2073-4409/12/14/1898FXTASfragile X premutation<i>FMR1</i>repeat expansion disordermovement disordercerebrovascular disease |
| spellingShingle | Jun Yi Wang Gerard J. Sonico Maria Jimena Salcedo-Arellano Randi J. Hagerman Veronica Martinez-Cerdeno A Postmortem MRI Study of Cerebrovascular Disease and Iron Content at End-Stage of Fragile X-Associated Tremor/Ataxia Syndrome Cells FXTAS fragile X premutation <i>FMR1</i> repeat expansion disorder movement disorder cerebrovascular disease |
| title | A Postmortem MRI Study of Cerebrovascular Disease and Iron Content at End-Stage of Fragile X-Associated Tremor/Ataxia Syndrome |
| title_full | A Postmortem MRI Study of Cerebrovascular Disease and Iron Content at End-Stage of Fragile X-Associated Tremor/Ataxia Syndrome |
| title_fullStr | A Postmortem MRI Study of Cerebrovascular Disease and Iron Content at End-Stage of Fragile X-Associated Tremor/Ataxia Syndrome |
| title_full_unstemmed | A Postmortem MRI Study of Cerebrovascular Disease and Iron Content at End-Stage of Fragile X-Associated Tremor/Ataxia Syndrome |
| title_short | A Postmortem MRI Study of Cerebrovascular Disease and Iron Content at End-Stage of Fragile X-Associated Tremor/Ataxia Syndrome |
| title_sort | postmortem mri study of cerebrovascular disease and iron content at end stage of fragile x associated tremor ataxia syndrome |
| topic | FXTAS fragile X premutation <i>FMR1</i> repeat expansion disorder movement disorder cerebrovascular disease |
| url | https://www.mdpi.com/2073-4409/12/14/1898 |
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