Clément Tarrano, Giuseppe Zito, Cécile Galléa, Cécile Delorme, Eavan M. McGovern, Cyril Atkinson‐Clement, Vanessa Brochard, Stéphane Thobois, Christine Tranchant, David Grabli, Bertrand Degos, Jean Christophe Corvol, Jean‐Michel Pedespan, Pierre Krystkowiak, Jean‐Luc Houeto, Adrian Degardin, Luc Defebvre, Mélanie Didier, Romain Valabrègue, Emmanuelle Apartis, Marie Vidailhet, Emmanuel Roze, Yulia Worbe
{"title":"Microstructure of the cerebellum and its afferent pathways underpins dystonia in myoclonus dystonia","authors":"Clément Tarrano, Giuseppe Zito, Cécile Galléa, Cécile Delorme, Eavan M. McGovern, Cyril Atkinson‐Clement, Vanessa Brochard, Stéphane Thobois, Christine Tranchant, David Grabli, Bertrand Degos, Jean Christophe Corvol, Jean‐Michel Pedespan, Pierre Krystkowiak, Jean‐Luc Houeto, Adrian Degardin, Luc Defebvre, Mélanie Didier, Romain Valabrègue, Emmanuelle Apartis, Marie Vidailhet, Emmanuel Roze, Yulia Worbe","doi":"10.1111/ene.16460","DOIUrl":null,"url":null,"abstract":"Background and PurposeMyoclonus dystonia due to a pathogenic variant in <jats:italic>SGCE</jats:italic> (MYC/DYT‐<jats:italic>SGCE</jats:italic>) is a rare condition involving a motor phenotype associating myoclonus and dystonia. Dysfunction within the networks relying on the cortex, cerebellum, and basal ganglia was presumed to underpin the clinical manifestations. However, the microarchitectural abnormalities within these structures and related pathways are unknown. Here, we investigated the microarchitectural brain abnormalities related to the motor phenotype in MYC/DYT‐<jats:italic>SGCE</jats:italic>.MethodsWe used neurite orientation dispersion and density imaging, a multicompartment tissue model of diffusion neuroimaging, to compare microarchitectural neurite organization in MYC/DYT‐<jats:italic>SGCE</jats:italic> patients and healthy volunteers (HVs). Neurite density index (NDI), orientation dispersion index (ODI), and isotropic volume fraction (ISOVF) were derived and correlated with the severity of motor symptoms. Fractional anisotropy (FA) and mean diffusivity (MD) derived from the diffusion tensor approach were also analyzed. In addition, we studied the pathways that correlated with motor symptom severity using tractography analysis.ResultsEighteen MYC/DYT‐<jats:italic>SGCE</jats:italic> patients and 24 HVs were analyzed. MYC/DYT‐<jats:italic>SGCE</jats:italic> patients showed an increase of ODI and a decrease of FA within their motor cerebellum. More severe dystonia was associated with lower ODI and NDI and higher FA within motor cerebellar cortex, as well as with lower NDI and higher ISOVF and MD within the corticopontocerebellar and spinocerebellar pathways. No association was found between myoclonus severity and diffusion parameters.ConclusionsIn MYC/DYT‐<jats:italic>SGCE</jats:italic>, we found microstructural reorganization of the motor cerebellum. Structural change in the cerebellar afferent pathways that relay inputs from the spinal cord and the cerebral cortex were specifically associated with the severity of dystonia.","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":null,"pages":null},"PeriodicalIF":4.5000,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Neurology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/ene.16460","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background and PurposeMyoclonus dystonia due to a pathogenic variant in SGCE (MYC/DYT‐SGCE) is a rare condition involving a motor phenotype associating myoclonus and dystonia. Dysfunction within the networks relying on the cortex, cerebellum, and basal ganglia was presumed to underpin the clinical manifestations. However, the microarchitectural abnormalities within these structures and related pathways are unknown. Here, we investigated the microarchitectural brain abnormalities related to the motor phenotype in MYC/DYT‐SGCE.MethodsWe used neurite orientation dispersion and density imaging, a multicompartment tissue model of diffusion neuroimaging, to compare microarchitectural neurite organization in MYC/DYT‐SGCE patients and healthy volunteers (HVs). Neurite density index (NDI), orientation dispersion index (ODI), and isotropic volume fraction (ISOVF) were derived and correlated with the severity of motor symptoms. Fractional anisotropy (FA) and mean diffusivity (MD) derived from the diffusion tensor approach were also analyzed. In addition, we studied the pathways that correlated with motor symptom severity using tractography analysis.ResultsEighteen MYC/DYT‐SGCE patients and 24 HVs were analyzed. MYC/DYT‐SGCE patients showed an increase of ODI and a decrease of FA within their motor cerebellum. More severe dystonia was associated with lower ODI and NDI and higher FA within motor cerebellar cortex, as well as with lower NDI and higher ISOVF and MD within the corticopontocerebellar and spinocerebellar pathways. No association was found between myoclonus severity and diffusion parameters.ConclusionsIn MYC/DYT‐SGCE, we found microstructural reorganization of the motor cerebellum. Structural change in the cerebellar afferent pathways that relay inputs from the spinal cord and the cerebral cortex were specifically associated with the severity of dystonia.
期刊介绍:
The European Journal of Neurology is the official journal of the European Academy of Neurology and covers all areas of clinical and basic research in neurology, including pre-clinical research of immediate translational value for new potential treatments. Emphasis is placed on major diseases of large clinical and socio-economic importance (dementia, stroke, epilepsy, headache, multiple sclerosis, movement disorders, and infectious diseases).