Microstructure of the cerebellum and its afferent pathways underpins dystonia in myoclonus dystonia

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

Microstructure of the cerebellum and its afferent pathways underpins dystonia in myoclonus dystonia

Eur J Neurol. 2024 Sep 10:e16460. doi: 10.1111/ene.16460. Online ahead of print.

Authors

Clément Tarrano^{1

2

3}, Giuseppe Zito⁴, Cécile Galléa^{1

5}, Cécile Delorme^{1

2}, Eavan M McGovern^{6

7}, Cyril Atkinson-Clement^{1

8}, Vanessa Brochard², Stéphane Thobois^{9

10}, Christine Tranchant^{11

12

13}, David Grabli^{1

2}, Bertrand Degos¹⁴, Jean Christophe Corvol^{1

2}, Jean-Michel Pedespan¹⁵, Pierre Krystkowiak¹⁶, Jean-Luc Houeto¹⁷, Adrian Degardin¹⁸, Luc Defebvre^{19

20}, Mélanie Didier^{1

5}, Romain Valabrègue^{1

5}, Emmanuelle Apartis^{1

3}, Marie Vidailhet^{1

2}, Emmanuel Roze^{1

2}, Yulia Worbe^{1

2

3}

Affiliations

¹ Paris Brain Institute, INSERM, CNRS, Sorbonne Université, Paris, France.
² Department of Neurology, Clinical Investigation Center for Neurosciences, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris, France.
³ Department of Clinical Neurophysiology, Saint-Antoine Hospital, Paris, France.
⁴ Swiss Paraplegic Research, Nottwil, Switzerland.
⁵ Paris Brain Institute, Centre de NeuroImagerie de Recherche, UMRS 975, CNRS UMR 7225, Sorbonne Université, Paris, France.
⁶ Department of Neurology, Beaumont Hospital, Dublin, Ireland.
⁷ School of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.
⁸ School of Medicine, University of Nottingham, Nottingham, UK.
⁹ Neurological Department C, Hopital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron, France.
¹⁰ Faculté de Medecine Lyon Sud Charles Mérieux, Université Claude Bernard Lyon 1, Lyon, France.
¹¹ Département de Neurologie, Hôpitaux Universitaires de Strasbourg, Hôpital de Hautepierre, Strasbourg, France.
¹² Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM U964/CNRS UMR7104, Université de Strasbourg, Illkirch, France.
¹³ Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg, Strasbourg, France.
¹⁴ Department of Neurology, Assistance Publique-Hôpitaux de Paris, Avicenne Hospital, Sorbonne Paris Nord, Bobigny, France.
¹⁵ Department of Neuropediatry, University Hospital of Pellegrin, Bordeaux, France.
¹⁶ Abu Dhabi Stem Cells Center, Abu Dhabi, UAE.
¹⁷ Department of Neurology, Centre Hospitalier Universitaire de Limoges, INSERM U1094, IRD U270, Epidemiology of Chronic Diseases in Tropical Zone, Institute of Epidemiology and Tropical Neurology, OmegaHealth, University of Limoges, Limoges, France.
¹⁸ Department of Neurology, Tourcoing Hospital, Tourcoing, France.
¹⁹ Centre Hospitalier Universitaire de Lille, INSERM U1172, Troubles Cognitifs Dégénératifs et Vasculaires, University of Lille, Lille, France.
²⁰ Lille Center of Excellence for Neurodegenerative Diseases, Lille, France.

PMID: 39254064
DOI: 10.1111/ene.16460

Abstract

Background and purpose: Myoclonus 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.

Methods: We 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.

Results: Eighteen 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.

Conclusions: In 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.

Keywords: cerebellum; diffusion tensor imaging; dystonia; myoclonus; neuroimaging.

Abstract

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