Chen Shihan, Ashton Catherine, Sakalla Rawan, Clement Guillemette, Planel Sophie, Bonnet Céline, Lamont Phillipa, Kulanthaivelu Karthik, Nalini Atchayaram, Houlden Henry, Duquette Antoine, Dicaire Marie-Josée, Agudo Pablo Iruzubieta, Martinez Javier Ruiz, de Lucas Enrique Marco, Berjon Rodrigo Sutil, Ceberio Jon Infante, Indelicato Elisabetta, Boesch Sylvia, Synofzik Matthis, Bender Benjamin, Danzi Matt C, Zuchner Stephan, Pellerin David, Brais Bernard, Renaud Mathilde, La Piana Roberta
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
Department of Neurology, Royal Perth Hospital, Perth, Western Australia.
medRxiv. 2024 May 16:2024.02.16.24302945. doi: 10.1101/2024.02.16.24302945.
GAA- ataxia (SCA27B) is a recently reported late-onset ataxia caused by a GAA repeat expansion in intron 1 of the gene. Initial studies revealed cerebellar atrophy in 74-97% of patients. A more detailed brain imaging characterization of GAA- ataxia is now needed to provide supportive diagnostic features and earlier disease recognition.
We performed a retrospective review of the brain MRIs of 35 patients (median age at MRI 63 years; range 28-88 years) from Quebec (n=27), Nancy (n=3), Perth (n=3) and Bengaluru (n=2) to assess the presence of atrophy in vermis, cerebellar hemispheres, brainstem, cerebral hemispheres, and corpus callosum, as well as white matter involvement. Following the identification of the superior cerebellar peduncles (SCPs) involvement, we verified its presence in 54 GAA- ataxia patients from four independent cohorts (Tübingen n=29; Donostia n=12; Innsbruck n=7; Cantabria n=6). To assess lobular atrophy, we performed quantitative cerebellar segmentation in 5 affected subjects with available 3D T1-weighted images and matched controls.
Cerebellar atrophy was documented in 33 subjects (94.3%). We observed SCP involvement in 22 subjects (62.8%) and confirmed this finding in 30/54 (55.6%) subjects from the validation cohorts. Cerebellar segmentation showed reduced mean volumes of lobules X and IV in the 5 affected individuals.
Cerebellar atrophy is a key feature of GAA- ataxia. The frequent SCP involvement observed in different cohorts may facilitate the diagnosis. The predominant involvement of lobule X correlates with the frequently observed downbeat nystagmus.
GAA相关性共济失调（SCA27B）是一种最近报道的迟发性共济失调，由该基因第1内含子中的GAA重复序列扩增引起。初步研究显示，74%至97%的患者存在小脑萎缩。现在需要对GAA相关性共济失调进行更详细的脑成像特征分析，以提供支持性诊断特征并更早地识别疾病。
我们对来自魁北克（n = 27）、南锡（n = 3）、珀斯（n = 3）和班加罗尔（n = 2）的35例患者（MRI检查时的中位年龄为63岁；范围为28至88岁）的脑部MRI进行了回顾性分析，以评估小脑蚓部、小脑半球、脑干、大脑半球和胼胝体是否存在萎缩，以及白质受累情况。在确定上小脑脚（SCPs）受累后，我们在来自四个独立队列的54例GAA相关性共济失调患者中（图宾根n = 29；多诺斯蒂亚n = 12；因斯布鲁克n = 7；坎塔布里亚n = 6）验证了其存在情况。为了评估小叶萎缩，我们对5例有可用3D T1加权图像的受累受试者和匹配的对照进行了定量小脑分割。
33例受试者（94.3%）记录有小脑萎缩。我们观察到22例受试者（62.8%）存在SCP受累，并在验证队列的30/54例（55.6%）受试者中证实了这一发现。小脑分割显示，5例受累个体的小叶X和小叶IV平均体积减小。
小脑萎缩是GAA相关性共济失调的关键特征。在不同队列中观察到的SCP频繁受累可能有助于诊断。小叶X的主要受累与经常观察到的下跳性眼球震颤相关。
