Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58th, The Second Zhongshan Road, Guangzhou, 518000, Guangdong, China.
Intensive Care Unit, The First Affiliated Hospital of Xiamen University, Xiamen, 361001, Fujian, China.
J Neurol. 2023 Sep;270(9):4466-4477. doi: 10.1007/s00415-023-11792-1. Epub 2023 Jun 8.
Clinical decision-making in spinocerebellar ataxia spectrum diseases (SCAs) has mainly been based on genetic tests, not considering the SCAs' imaging and clinical heterogenicity.
To identify SCAs phenogroups by analysis and hierarchical clustering of infratentorial morphological MRI for unveiling pathophysiological differences among common SCA subtypes.
We prospectively enrolled 119 (62 women; mean age 37 years) genetically diagnosed SCAs (SCA1 n = 21, SCA2 n = 10, symptomatic SCA3 n = 59, presymptomatic SCA3 n = 22, SCA6 n = 7) and 35 healthy controls (HCs). All patients underwent MRI and detailed neurological and neuropsychology examinations. The width of each cerebellar peduncle (CP) and anteroposterior diameter of the spinal cord and pontine were measured. Twenty-five SCAs patients (15 women; mean age 35 years) were followed for at least a year (17 (15, 24) months), whose MRI and the Scale for the Assessment and Rating of Ataxia (SARA) were collected.
Infratentorial morphological MRI measurements could significantly discriminate SCAs from HCs, even among SCA subtypes. Two mutually exclusive and clinically distinct phenogroups were identified. Despite similar (CAG), phenogroup 1 (n = 66, 55.5%) presented more atrophied infratentorial brain structures and more severe clinical symptoms with older age and earlier age of onset when compared with phenogroup 2. More importantly, all SCA2, most of SCA1 (76%), and symptomatic SCA3 (68%) were classified into phenogroup 1, whereas all SCA6 and all presymptomatic SCA3 were in phenogroup 2. The right middle CP had the highest diagnostic value in predicting phenogroup 2 (AUC = 0.99; P < 0.01) with high specificity (95%). Consistent with the significantly increased SARA (7.5 vs 10, P = 0.021), the bilateral inferior CP, spinal cord, and pontine tegmentum were more atrophy during the follow-up (P < 0.05).
SCAs were with significant infratentorial brain atrophy than HCs. We identified two different SCAs phenogroups associated with substantial differences in infratentorial brain atrophy, clinical presentation, and may reflect the underlying molecular profiles to some extent, paving the way for a more personalized diagnostic and treatment approach.
在脊髓小脑共济失调谱系疾病（SCA）的临床决策中，主要基于基因检测，而不考虑 SCA 的影像学和临床异质性。
通过分析和层次聚类小脑形态学 MRI 来确定 SCA 的表型群，以揭示常见 SCA 亚型之间的病理生理学差异。
我们前瞻性纳入 119 名（62 名女性；平均年龄 37 岁）基因诊断的 SCA（SCA1 n=21，SCA2 n=10，症状性 SCA3 n=59，无症状性 SCA3 n=22，SCA6 n=7）和 35 名健康对照者（HCs）。所有患者均行 MRI 和详细的神经和神经心理学检查。测量每个小脑脚（CP）的宽度和脊髓及脑桥的前后径。25 名 SCA 患者（15 名女性；平均年龄 35 岁）至少随访 1 年（17（15，24）个月），收集其 MRI 和共济失调评估量表（SARA）。
小脑形态 MRI 测量可显著区分 SCA 与 HCs，甚至在 SCA 亚型之间也是如此。确定了两个相互排斥且临床特征不同的表型群。尽管（CAG）相似，但表型群 1（n=66，55.5%）表现出更明显的小脑脑结构萎缩和更严重的临床症状，年龄更大，发病年龄更早。更重要的是，所有 SCA2、大多数 SCA1（76%）和症状性 SCA3（68%）均被归类为表型群 1，而所有 SCA6 和所有无症状性 SCA3 均为表型群 2。右侧 CP 中部在预测表型群 2 方面具有最高的诊断价值（AUC=0.99；P<0.01），且特异性高（95%）。与 SARA 明显增加（7.5 与 10，P=0.021）一致，双侧 CP 下部、脊髓和脑桥被盖在随访期间更萎缩（P<0.05）。
SCA 比 HCs 有明显的小脑脑萎缩。我们确定了两个不同的 SCA 表型群，与小脑脑萎缩存在显著差异，临床表现不同，可能在一定程度上反映了潜在的分子特征，为更个性化的诊断和治疗方法铺平了道路。
