Sobana Siti Aminah, Huda Fathul, Hermawan Robby, Sribudiani Yunia, Koan Tan Siauw, Dian Sofiati, Ong Paulus Anam, Dahlan Nushrotul Lailiyya, Utami Nastiti, Pusparini Iin, Gamayani Uni, Mohamed Ibrahim Norlinah, Achmad Tri Hanggono
Department of Neurology, Faculty of Medicine, Dr. Hasan Sadikin Central General Hospital/Universitas Padjadjaran, Bandung, Indonesia.
Research Center of Medical Genetics, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia.
Front Neurol. 2022 Jun 29;13:912592. doi: 10.3389/fneur.2022.912592. eCollection 2022.
Spinocerebellar 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.
The 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).
We evaluated 7 subjects from this SCA3 family, including 3 subjects with SCA3 and 4 unaffected subjects. The volumetric evaluation revealed smaller brain volumes ( < 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).
Brain 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.
3型脊髓小脑共济失调（SCA3）是一种成年发病的常染色体显性神经退行性疾病。它由ATXN3基因中CAG重复序列的扩增引起，随后会影响脑结构。这种脑变化可以通过脑MRI容积分析来评估。然而，已发表的脑容积研究结果并不一致。在此，我们报告了对一个SCA 3患者家系的MRI脑容积分析，其中包括症状前和有症状的患者。
该研究纳入了一个大型的六代SCA 3家系中的患病和未患病成员，通过多聚谷氨酰胺/ CAG重复序列扩增分析、桑格测序和聚合酶链反应进行基因确认。使用共济失调评估和评分量表（SARA）进行临床评估。受试者的大脑使用3.0-T MRI和3D T1 BRAVO序列进行扫描。由2名独立的神经放射科医生进行评估。使用FreeSurfer和CERES（用于小脑）进行自动容积分析。
我们评估了这个SCA3家系的7名受试者，包括3名SCA3患者和4名未患病受试者。容积评估显示，在胼胝体、小脑小叶I-II、小叶IV、小叶VIIB和小叶IX的小脑体积；以及小叶IV和VIIIA的小脑灰质体积中，病理/扩增CAG重复序列组（SCA3）的脑体积较小（<0.05）。
SCA3受试者的脑MRI容积分析显示，包括胼胝体和几个小脑小叶灰质体积在内的多个脑区脑体积较小。
