Structural alterations of spinocerebellar ataxias type 3: from pre-symptomatic to symptomatic stage
Objectives To investigate and characterize the structural alterations of the brain in SCA3, and their correlations with the scale for the assessment and rating of ataxia (SARA) and normal brain ATXN3 expression. Methods We performed multimodal analyses in 52 SCA3 (15 pre-symptomatic) and healthy con...
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| Veröffentlicht in: | European radiology 2023-04, Vol.33 (4), p.2881-2894 |
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| creator | Qiu, Haishan Wu, Chao Liang, Jiahui Hu, Manshi Chen, Yingqian Huang, Zihuan Yang, Zhiyun Zhao, Jing Chu, Jianping |
| description | Objectives
To investigate and characterize the structural alterations of the brain in SCA3, and their correlations with the scale for the assessment and rating of ataxia (SARA) and normal brain
ATXN3
expression.
Methods
We performed multimodal analyses in 52 SCA3 (15 pre-symptomatic) and healthy controls (HCs) (
n
= 35) to assess the abnormalities of gray and white matter (WM) of the cerebrum, brainstem, and cerebellum via FreeSurfer, SUIT, and TBSS, and their associations with disease severity. Twenty SCA3 patients (5 pre- and 15 symptomatic) were followed for at least a year. Besides, we uncovered the normal pattern of brain
ATXN3
spatial distribution.
Results
Pre-symptomatic patients showed only WM damage, mainly in the cerebellar peduncles, compared to HCs. In the advanced stage, the WM damage followed a caudal-rostral pattern. Meanwhile, continuous nonlinear structure damage was characterized by brainstem volumetric reduction and relatively symmetric cerebellar and basal ganglia atrophy but spared the cerebral cortex, partially explained by the
ATXN3
overexpression. The bilateral pallidum, brainstem, and cerebellar peduncles demonstrated a very large effect size. Besides, all these alterations were significantly correlated with SARA; the pons (
r
= −0.65) and superior cerebellar peduncle (
r
= −0.68) volume demonstrated a higher correlation than the cerebellum with SARA. The longitudinal study further uncovered progressive atrophy of pons in symptomatic SCA3.
Conclusions
Significant WM damage starts before the ataxia onset. The bilateral pallidum, brainstem, and cerebellar peduncles are the most vulnerable targets. The volume of pons appears to be the most promising imaging biomarker for a longitudinal study.
Trial registration
ClinicalTrial ID: ChiCTR2100045857 (
http://www.chictr.org.cn/edit.aspx?pid=55652&htm=4
)
Key Points
•
Pre- SCA3 showed WM damage mainly in cerebellar peduncles. Continuous brain damage was characterized by brainstem, widespread, and relatively symmetric cerebellar and basal ganglia atrophy.
•
Volumetric abnormalities were most evident in the bilateral pallidum, brainstem, and cerebellar peduncles in SCA3.
•
The volume of pons might identify the disease progression longitudinally. |
| doi_str_mv | 10.1007/s00330-022-09214-3 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2735865601</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2787049692</sourcerecordid><originalsourceid>FETCH-LOGICAL-c375t-8f6b986e73ba5693c7eae2c8a0b4056156cacf79c4d87f44245ddda0e6f429293</originalsourceid><addsrcrecordid>eNp9kc1O3TAQha0KVOC2L9AFssSmm5TxT-y4O4QKrYTEArq2HGeCgpI4tR2p9-0xXKCIRVe2Nd85c-RDyBcG3xiAPk0AQkAFnFdgOJOV-EAOmRS8YtDIvTf3A3KU0j0AGCb1R3IglNDAND8k_ibH1ec1upG6MWN0eQhzoqGnaRnm4DFii-PoInXZ_R1conm7IBXfaR_DRJeIVdpOSw5TUXqaA337TNnd4Sey37sx4efnc0N-X_y4Pf9ZXV1f_jo_u6q80HWuml61plGoRetqZYTX6JD7xkEroVasVt75Xhsvu0b3UnJZd13nAFUvueFGbMjXne8Sw58VU7bTkPxj-BnDmizXom5UrYAV9OQdeh_WOJd0hWo0SKMMLxTfUT6GlCL2donD5OLWMrCPFdhdBbZUYJ8qsKKIjp-t13bC7lXy8ucFEDsgldF8h_Hf7v_YPgAYe5JN</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2787049692</pqid></control><display><type>article</type><title>Structural alterations of spinocerebellar ataxias type 3: from pre-symptomatic to symptomatic stage</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Qiu, Haishan ; Wu, Chao ; Liang, Jiahui ; Hu, Manshi ; Chen, Yingqian ; Huang, Zihuan ; Yang, Zhiyun ; Zhao, Jing ; Chu, Jianping</creator><creatorcontrib>Qiu, Haishan ; Wu, Chao ; Liang, Jiahui ; Hu, Manshi ; Chen, Yingqian ; Huang, Zihuan ; Yang, Zhiyun ; Zhao, Jing ; Chu, Jianping</creatorcontrib><description>Objectives
To investigate and characterize the structural alterations of the brain in SCA3, and their correlations with the scale for the assessment and rating of ataxia (SARA) and normal brain
ATXN3
expression.
Methods
We performed multimodal analyses in 52 SCA3 (15 pre-symptomatic) and healthy controls (HCs) (
n
= 35) to assess the abnormalities of gray and white matter (WM) of the cerebrum, brainstem, and cerebellum via FreeSurfer, SUIT, and TBSS, and their associations with disease severity. Twenty SCA3 patients (5 pre- and 15 symptomatic) were followed for at least a year. Besides, we uncovered the normal pattern of brain
ATXN3
spatial distribution.
Results
Pre-symptomatic patients showed only WM damage, mainly in the cerebellar peduncles, compared to HCs. In the advanced stage, the WM damage followed a caudal-rostral pattern. Meanwhile, continuous nonlinear structure damage was characterized by brainstem volumetric reduction and relatively symmetric cerebellar and basal ganglia atrophy but spared the cerebral cortex, partially explained by the
ATXN3
overexpression. The bilateral pallidum, brainstem, and cerebellar peduncles demonstrated a very large effect size. Besides, all these alterations were significantly correlated with SARA; the pons (
r
= −0.65) and superior cerebellar peduncle (
r
= −0.68) volume demonstrated a higher correlation than the cerebellum with SARA. The longitudinal study further uncovered progressive atrophy of pons in symptomatic SCA3.
Conclusions
Significant WM damage starts before the ataxia onset. The bilateral pallidum, brainstem, and cerebellar peduncles are the most vulnerable targets. The volume of pons appears to be the most promising imaging biomarker for a longitudinal study.
Trial registration
ClinicalTrial ID: ChiCTR2100045857 (
http://www.chictr.org.cn/edit.aspx?pid=55652&htm=4
)
Key Points
•
Pre- SCA3 showed WM damage mainly in cerebellar peduncles. Continuous brain damage was characterized by brainstem, widespread, and relatively symmetric cerebellar and basal ganglia atrophy.
•
Volumetric abnormalities were most evident in the bilateral pallidum, brainstem, and cerebellar peduncles in SCA3.
•
The volume of pons might identify the disease progression longitudinally.</description><identifier>ISSN: 1432-1084</identifier><identifier>ISSN: 0938-7994</identifier><identifier>EISSN: 1432-1084</identifier><identifier>DOI: 10.1007/s00330-022-09214-3</identifier><identifier>PMID: 36370172</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Abnormalities ; Ataxia ; Atrophy ; Atrophy - diagnostic imaging ; Atrophy - pathology ; Basal ganglia ; Biomarkers ; Brain ; Brain - diagnostic imaging ; Brain - pathology ; Brain damage ; Brain injury ; Brain stem ; Cerebellum ; Cerebellum - diagnostic imaging ; Cerebellum - pathology ; Cerebral cortex ; Cerebrum ; Correlation analysis ; Damage patterns ; Diagnostic Radiology ; Ganglia ; Globus pallidus ; Humans ; Imaging ; Internal Medicine ; Interventional Radiology ; Longitudinal Studies ; Machado-Joseph Disease - diagnostic imaging ; Machado-Joseph Disease - genetics ; Machado-Joseph Disease - pathology ; Magnetic Resonance Imaging - methods ; Medicine ; Medicine & Public Health ; Neuro ; Neuroimaging ; Neuroradiology ; Pons ; Radiology ; Spatial distribution ; Spinocerebellar ataxia ; Substantia alba ; Superior cerebellar peduncle ; Ultrasound</subject><ispartof>European radiology, 2023-04, Vol.33 (4), p.2881-2894</ispartof><rights>The Author(s), under exclusive licence to European Society of Radiology 2022. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2022. The Author(s), under exclusive licence to European Society of Radiology.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-8f6b986e73ba5693c7eae2c8a0b4056156cacf79c4d87f44245ddda0e6f429293</citedby><cites>FETCH-LOGICAL-c375t-8f6b986e73ba5693c7eae2c8a0b4056156cacf79c4d87f44245ddda0e6f429293</cites><orcidid>0000-0001-5483-2169</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00330-022-09214-3$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00330-022-09214-3$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36370172$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Qiu, Haishan</creatorcontrib><creatorcontrib>Wu, Chao</creatorcontrib><creatorcontrib>Liang, Jiahui</creatorcontrib><creatorcontrib>Hu, Manshi</creatorcontrib><creatorcontrib>Chen, Yingqian</creatorcontrib><creatorcontrib>Huang, Zihuan</creatorcontrib><creatorcontrib>Yang, Zhiyun</creatorcontrib><creatorcontrib>Zhao, Jing</creatorcontrib><creatorcontrib>Chu, Jianping</creatorcontrib><title>Structural alterations of spinocerebellar ataxias type 3: from pre-symptomatic to symptomatic stage</title><title>European radiology</title><addtitle>Eur Radiol</addtitle><addtitle>Eur Radiol</addtitle><description>Objectives
To investigate and characterize the structural alterations of the brain in SCA3, and their correlations with the scale for the assessment and rating of ataxia (SARA) and normal brain
ATXN3
expression.
Methods
We performed multimodal analyses in 52 SCA3 (15 pre-symptomatic) and healthy controls (HCs) (
n
= 35) to assess the abnormalities of gray and white matter (WM) of the cerebrum, brainstem, and cerebellum via FreeSurfer, SUIT, and TBSS, and their associations with disease severity. Twenty SCA3 patients (5 pre- and 15 symptomatic) were followed for at least a year. Besides, we uncovered the normal pattern of brain
ATXN3
spatial distribution.
Results
Pre-symptomatic patients showed only WM damage, mainly in the cerebellar peduncles, compared to HCs. In the advanced stage, the WM damage followed a caudal-rostral pattern. Meanwhile, continuous nonlinear structure damage was characterized by brainstem volumetric reduction and relatively symmetric cerebellar and basal ganglia atrophy but spared the cerebral cortex, partially explained by the
ATXN3
overexpression. The bilateral pallidum, brainstem, and cerebellar peduncles demonstrated a very large effect size. Besides, all these alterations were significantly correlated with SARA; the pons (
r
= −0.65) and superior cerebellar peduncle (
r
= −0.68) volume demonstrated a higher correlation than the cerebellum with SARA. The longitudinal study further uncovered progressive atrophy of pons in symptomatic SCA3.
Conclusions
Significant WM damage starts before the ataxia onset. The bilateral pallidum, brainstem, and cerebellar peduncles are the most vulnerable targets. The volume of pons appears to be the most promising imaging biomarker for a longitudinal study.
Trial registration
ClinicalTrial ID: ChiCTR2100045857 (
http://www.chictr.org.cn/edit.aspx?pid=55652&htm=4
)
Key Points
•
Pre- SCA3 showed WM damage mainly in cerebellar peduncles. Continuous brain damage was characterized by brainstem, widespread, and relatively symmetric cerebellar and basal ganglia atrophy.
•
Volumetric abnormalities were most evident in the bilateral pallidum, brainstem, and cerebellar peduncles in SCA3.
•
The volume of pons might identify the disease progression longitudinally.</description><subject>Abnormalities</subject><subject>Ataxia</subject><subject>Atrophy</subject><subject>Atrophy - diagnostic imaging</subject><subject>Atrophy - pathology</subject><subject>Basal ganglia</subject><subject>Biomarkers</subject><subject>Brain</subject><subject>Brain - diagnostic imaging</subject><subject>Brain - pathology</subject><subject>Brain damage</subject><subject>Brain injury</subject><subject>Brain stem</subject><subject>Cerebellum</subject><subject>Cerebellum - diagnostic imaging</subject><subject>Cerebellum - pathology</subject><subject>Cerebral cortex</subject><subject>Cerebrum</subject><subject>Correlation analysis</subject><subject>Damage patterns</subject><subject>Diagnostic Radiology</subject><subject>Ganglia</subject><subject>Globus pallidus</subject><subject>Humans</subject><subject>Imaging</subject><subject>Internal Medicine</subject><subject>Interventional Radiology</subject><subject>Longitudinal Studies</subject><subject>Machado-Joseph Disease - diagnostic imaging</subject><subject>Machado-Joseph Disease - genetics</subject><subject>Machado-Joseph Disease - pathology</subject><subject>Magnetic Resonance Imaging - methods</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Neuro</subject><subject>Neuroimaging</subject><subject>Neuroradiology</subject><subject>Pons</subject><subject>Radiology</subject><subject>Spatial distribution</subject><subject>Spinocerebellar ataxia</subject><subject>Substantia alba</subject><subject>Superior cerebellar peduncle</subject><subject>Ultrasound</subject><issn>1432-1084</issn><issn>0938-7994</issn><issn>1432-1084</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kc1O3TAQha0KVOC2L9AFssSmm5TxT-y4O4QKrYTEArq2HGeCgpI4tR2p9-0xXKCIRVe2Nd85c-RDyBcG3xiAPk0AQkAFnFdgOJOV-EAOmRS8YtDIvTf3A3KU0j0AGCb1R3IglNDAND8k_ibH1ec1upG6MWN0eQhzoqGnaRnm4DFii-PoInXZ_R1conm7IBXfaR_DRJeIVdpOSw5TUXqaA337TNnd4Sey37sx4efnc0N-X_y4Pf9ZXV1f_jo_u6q80HWuml61plGoRetqZYTX6JD7xkEroVasVt75Xhsvu0b3UnJZd13nAFUvueFGbMjXne8Sw58VU7bTkPxj-BnDmizXom5UrYAV9OQdeh_WOJd0hWo0SKMMLxTfUT6GlCL2donD5OLWMrCPFdhdBbZUYJ8qsKKIjp-t13bC7lXy8ucFEDsgldF8h_Hf7v_YPgAYe5JN</recordid><startdate>20230401</startdate><enddate>20230401</enddate><creator>Qiu, Haishan</creator><creator>Wu, Chao</creator><creator>Liang, Jiahui</creator><creator>Hu, Manshi</creator><creator>Chen, Yingqian</creator><creator>Huang, Zihuan</creator><creator>Yang, Zhiyun</creator><creator>Zhao, Jing</creator><creator>Chu, Jianping</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QO</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-5483-2169</orcidid></search><sort><creationdate>20230401</creationdate><title>Structural alterations of spinocerebellar ataxias type 3: from pre-symptomatic to symptomatic stage</title><author>Qiu, Haishan ; Wu, Chao ; Liang, Jiahui ; Hu, Manshi ; Chen, Yingqian ; Huang, Zihuan ; Yang, Zhiyun ; Zhao, Jing ; Chu, Jianping</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-8f6b986e73ba5693c7eae2c8a0b4056156cacf79c4d87f44245ddda0e6f429293</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Abnormalities</topic><topic>Ataxia</topic><topic>Atrophy</topic><topic>Atrophy - diagnostic imaging</topic><topic>Atrophy - pathology</topic><topic>Basal ganglia</topic><topic>Biomarkers</topic><topic>Brain</topic><topic>Brain - diagnostic imaging</topic><topic>Brain - pathology</topic><topic>Brain damage</topic><topic>Brain injury</topic><topic>Brain stem</topic><topic>Cerebellum</topic><topic>Cerebellum - diagnostic imaging</topic><topic>Cerebellum - pathology</topic><topic>Cerebral cortex</topic><topic>Cerebrum</topic><topic>Correlation analysis</topic><topic>Damage patterns</topic><topic>Diagnostic Radiology</topic><topic>Ganglia</topic><topic>Globus pallidus</topic><topic>Humans</topic><topic>Imaging</topic><topic>Internal Medicine</topic><topic>Interventional Radiology</topic><topic>Longitudinal Studies</topic><topic>Machado-Joseph Disease - diagnostic imaging</topic><topic>Machado-Joseph Disease - genetics</topic><topic>Machado-Joseph Disease - pathology</topic><topic>Magnetic Resonance Imaging - methods</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Neuro</topic><topic>Neuroimaging</topic><topic>Neuroradiology</topic><topic>Pons</topic><topic>Radiology</topic><topic>Spatial distribution</topic><topic>Spinocerebellar ataxia</topic><topic>Substantia alba</topic><topic>Superior cerebellar peduncle</topic><topic>Ultrasound</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Qiu, Haishan</creatorcontrib><creatorcontrib>Wu, Chao</creatorcontrib><creatorcontrib>Liang, Jiahui</creatorcontrib><creatorcontrib>Hu, Manshi</creatorcontrib><creatorcontrib>Chen, Yingqian</creatorcontrib><creatorcontrib>Huang, Zihuan</creatorcontrib><creatorcontrib>Yang, Zhiyun</creatorcontrib><creatorcontrib>Zhao, Jing</creatorcontrib><creatorcontrib>Chu, Jianping</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>European radiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Qiu, Haishan</au><au>Wu, Chao</au><au>Liang, Jiahui</au><au>Hu, Manshi</au><au>Chen, Yingqian</au><au>Huang, Zihuan</au><au>Yang, Zhiyun</au><au>Zhao, Jing</au><au>Chu, Jianping</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Structural alterations of spinocerebellar ataxias type 3: from pre-symptomatic to symptomatic stage</atitle><jtitle>European radiology</jtitle><stitle>Eur Radiol</stitle><addtitle>Eur Radiol</addtitle><date>2023-04-01</date><risdate>2023</risdate><volume>33</volume><issue>4</issue><spage>2881</spage><epage>2894</epage><pages>2881-2894</pages><issn>1432-1084</issn><issn>0938-7994</issn><eissn>1432-1084</eissn><abstract>Objectives
To investigate and characterize the structural alterations of the brain in SCA3, and their correlations with the scale for the assessment and rating of ataxia (SARA) and normal brain
ATXN3
expression.
Methods
We performed multimodal analyses in 52 SCA3 (15 pre-symptomatic) and healthy controls (HCs) (
n
= 35) to assess the abnormalities of gray and white matter (WM) of the cerebrum, brainstem, and cerebellum via FreeSurfer, SUIT, and TBSS, and their associations with disease severity. Twenty SCA3 patients (5 pre- and 15 symptomatic) were followed for at least a year. Besides, we uncovered the normal pattern of brain
ATXN3
spatial distribution.
Results
Pre-symptomatic patients showed only WM damage, mainly in the cerebellar peduncles, compared to HCs. In the advanced stage, the WM damage followed a caudal-rostral pattern. Meanwhile, continuous nonlinear structure damage was characterized by brainstem volumetric reduction and relatively symmetric cerebellar and basal ganglia atrophy but spared the cerebral cortex, partially explained by the
ATXN3
overexpression. The bilateral pallidum, brainstem, and cerebellar peduncles demonstrated a very large effect size. Besides, all these alterations were significantly correlated with SARA; the pons (
r
= −0.65) and superior cerebellar peduncle (
r
= −0.68) volume demonstrated a higher correlation than the cerebellum with SARA. The longitudinal study further uncovered progressive atrophy of pons in symptomatic SCA3.
Conclusions
Significant WM damage starts before the ataxia onset. The bilateral pallidum, brainstem, and cerebellar peduncles are the most vulnerable targets. The volume of pons appears to be the most promising imaging biomarker for a longitudinal study.
Trial registration
ClinicalTrial ID: ChiCTR2100045857 (
http://www.chictr.org.cn/edit.aspx?pid=55652&htm=4
)
Key Points
•
Pre- SCA3 showed WM damage mainly in cerebellar peduncles. Continuous brain damage was characterized by brainstem, widespread, and relatively symmetric cerebellar and basal ganglia atrophy.
•
Volumetric abnormalities were most evident in the bilateral pallidum, brainstem, and cerebellar peduncles in SCA3.
•
The volume of pons might identify the disease progression longitudinally.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>36370172</pmid><doi>10.1007/s00330-022-09214-3</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0001-5483-2169</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1432-1084 |
| ispartof | European radiology, 2023-04, Vol.33 (4), p.2881-2894 |
| issn | 1432-1084 0938-7994 1432-1084 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2735865601 |
| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Abnormalities Ataxia Atrophy Atrophy - diagnostic imaging Atrophy - pathology Basal ganglia Biomarkers Brain Brain - diagnostic imaging Brain - pathology Brain damage Brain injury Brain stem Cerebellum Cerebellum - diagnostic imaging Cerebellum - pathology Cerebral cortex Cerebrum Correlation analysis Damage patterns Diagnostic Radiology Ganglia Globus pallidus Humans Imaging Internal Medicine Interventional Radiology Longitudinal Studies Machado-Joseph Disease - diagnostic imaging Machado-Joseph Disease - genetics Machado-Joseph Disease - pathology Magnetic Resonance Imaging - methods Medicine Medicine & Public Health Neuro Neuroimaging Neuroradiology Pons Radiology Spatial distribution Spinocerebellar ataxia Substantia alba Superior cerebellar peduncle Ultrasound |
| title | Structural alterations of spinocerebellar ataxias type 3: from pre-symptomatic to symptomatic stage |
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