Regional Brain and Spinal Cord Volume Loss in Spinocerebellar Ataxia Type 3

Faber, Jennifer; Schaprian, Tamara; Berkan, Koyak; Reetz, Kathrin; França, Marcondes Cavalcante; Rezende, Thiago Junqueira Ribeiro de; Jiang, Hong; Liao, Weihua; Warrenburg, Bart van de; Gaalen, Judith van; Dürr, Alexandra; Mochel, Fanny; Giunti, Paola; García-Moreno, Héctor; Schoels, Ludger; Hengel, Holger; Synofzik, Matthis; Bender, Benjamín; Öz, Gülin; Joers, James M.; Vries, Jereon J. de; Kang, Jun Suk; Timmann-Braun, Dagmar; Jacobi, Heike; Infante, Jon; Joules, Richard; Romanzetti, Sandro; Diedrichsen, Jörn; Schmid, Matthias; Wolz, Robin; Klockgether, Thomas

doi:10.1002/mds.28610

Cited by 46 publications

(62 citation statements)

References 36 publications

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“…This may provide support for the concept that these regions show altered neuronal activity due to disconnection (or other downstream network effects) from cerebellum and striatum, two core structures that are directly affected by local pathology. Regarding structural disconnection, studies have also found evidence for affected (infratentorial) white matter structures, and an association with disease progression and ataxia severity ( Faber et al, 2021 , Rezende et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

A resting-state fMRI pattern of spinocerebellar ataxia type 3 and comparison with 18F-FDG PET

Horn

Meles

Kok

et al. 2022

NeuroImage: Clinical

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Section: Discussionmentioning

confidence: 99%

A resting-state fMRI pattern of spinocerebellar ataxia type 3 and comparison with 18F-FDG PET

Horn

Meles

Kok

et al. 2022

NeuroImage: Clinical

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“…Guo et al studied 47 SCA3 subjects in a Chinese population and showed progressive atrophy in cerebellar gray matter and several cerebrum regions ( 22 ). Faber et al gathered 210 SCA3 subjects from 8 countries (Brazil, China, France, Germany, Netherland, Spain, UK, and US) and found atrophy in cerebellum, brainstem, thalamus, basal ganglia with dilation of ventricle ( 23 ). Hernandez-Castillo et al studied 17 SCA3 patients from Mexican population and found atrophy in cerebellum, pons and left lingual gyrus ( 24 ).…”

Section: Discussionmentioning

confidence: 99%

“…Recent publications have reported variable findings in the volumetry of various anatomical brain structures in patients with SCA3 (17)(18)(19)(20)(21)(22)(23)(24). One recent study reported that patients with SCA 3 had decreased cerebellar and cerebral volumes, and also the basal ganglia, gray matter and the thalamus (18).…”

Section: Introductionmentioning

confidence: 99%

Brain MRI Volumetry Analysis in an Indonesian Family of SCA 3 Patients: A Case-Based Study

Sobana

Huda

Hermawan³

et al. 2022

Front. Neurol.

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IntroductionSpinocerebellar ataxia type-3 (SCA3) is an adult-onset autosomal dominant neurodegenerative disease. It is caused by expanding of CAG repeat in ATXN3 gene that later on would affect brain structures. This brain changes could be evaluated using brain MRI volumetric. However, findings across published brain volumetric studies have been inconsistent. Here, we report MRI brain volumetric analysis in a family of SCA 3 patients, which included pre-symptomatic and symptomatic patients.MethodologyThe study included affected and unaffected members from a large six-generation family of SCA 3, genetically confirmed using PolyQ/CAG repeat expansion analysis, Sanger sequencing, and PCR. Clinical evaluation was performed using Scale for the Assessment and Rating of Ataxia (SARA). Subjects' brains were scanned using 3.0-T MRI with a 3D T1 BRAVO sequence. Evaluations were performed by 2 independent neuroradiologists. An automated volumetric analysis was performed using FreeSurfer and CERES (for the cerebellum).ResultWe evaluated 7 subjects from this SCA3 family, including 3 subjects with SCA3 and 4 unaffected subjects. The volumetric evaluation revealed smaller brain volumes (p < 0.05) in the corpus callosum, cerebellar volume of lobules I-II, lobule IV, lobule VIIB and lobule IX; and in cerebellar gray matter volume of lobule IV, and VIIIA; in the pathologic/expanded CAG repeat group (SCA3).ConclusionBrain MRI volumetry of SCA3 subjects showed smaller brain volumes in multiple brain regions including the corpus callosum and gray matter volumes of several cerebellar lobules.

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“…Aside from the common features mentioned above, SCA3 can be distinguished from other SCAs by the presence of pyramidal and extrapyramidal motor dysfunctions. Degeneration in SCA3 patient brains is often seen in the dentate neurons of the cerebellum, pontine nuclei, brainstem, and basal ganglia [103][104][105]. As with most SCA diseases, SCA3 also includes a number of non-motor symptoms-including sleep and mood disorders, depression, as well as cognitive and other psychiatric disturbances [106,107].…”

Section: Spinocerebellar Ataxia Type 3 (Sca3)mentioning

confidence: 99%

Polyglutamine Ataxias: Our Current Molecular Understanding and What the Future Holds for Antisense Therapies

McIntosh

Wilton

et al. 2021

Biomedicines

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Polyglutamine (polyQ) ataxias are a heterogenous group of neurological disorders all caused by an expanded CAG trinucleotide repeat located in the coding region of each unique causative gene. To date, polyQ ataxias encompass six disorders: spinocerebellar ataxia types 1, 2, 3, 6, 7, and 17 and account for a larger group of disorders simply known as polyglutamine disorders, which also includes Huntington’s disease. These diseases are typically characterised by progressive ataxia, speech and swallowing difficulties, lack of coordination and gait, and are unfortunately fatal in nature, with the exception of SCA6. All the polyQ spinocerebellar ataxias have a hallmark feature of neuronal aggregations and share many common pathogenic mechanisms, such as mitochondrial dysfunction, impaired proteasomal function, and autophagy impairment. Currently, therapeutic options are limited, with no available treatments that slow or halt disease progression. Here, we discuss the common molecular and clinical presentations of polyQ spinocerebellar ataxias. We will also discuss the promising antisense oligonucleotide therapeutics being developed as treatments for these devastating diseases. With recent advancements and therapeutic approvals of various antisense therapies, it is envisioned that some of the studies reviewed may progress into clinical trials and beyond.

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Regional Brain and Spinal Cord Volume Loss in Spinocerebellar Ataxia Type 3

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 46 publications

References 36 publications

A resting-state fMRI pattern of spinocerebellar ataxia type 3 and comparison with 18F-FDG PET

A resting-state fMRI pattern of spinocerebellar ataxia type 3 and comparison with 18F-FDG PET

Brain MRI Volumetry Analysis in an Indonesian Family of SCA 3 Patients: A Case-Based Study

Polyglutamine Ataxias: Our Current Molecular Understanding and What the Future Holds for Antisense Therapies

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