背景:脊髓小脑性共济失调谱系疾病(SCAs)的临床决策主要基于基因测试,不考虑SCA成像和临床异质性。
目的:通过对幕下形态学MRI的分析和层次聚类来识别SCA表型群,以揭示常见SCA亚型之间的病理生理差异。
方法:我们前瞻性招募了119名(62名女性;平均年龄37岁)基因诊断的SCA(SCA1n=21,SCA2n=10,有症状的SCA3n=59,有症状的SCA3n=22,SCA6n=7)和35名健康对照(HCs)。所有患者均接受MRI和详细的神经和神经心理学检查。测量每个小脑柄(CP)的宽度以及脊髓和脑桥的前后直径。25名SCA患者(15名女性;平均年龄35岁)随访至少一年(17(15,24)个月),收集其MRI和共济失调评估和等级量表(SARA)。
结果:幕下形态学MRI测量可以显着区分SCAs和HCs,甚至在SCA亚型之间。确定了两个相互排斥且临床上不同的表型。尽管类似(CAG)n,与表型组2相比,表型组1(n=66,55.5%)表现出更多的幕下大脑结构萎缩和更严重的临床症状。更重要的是,所有SCA2,大部分SCA1(76%),和有症状的SCA3(68%)被分类为表型组1,而所有SCA6和所有有症状的SCA3均为表型组2.右中CP在预测表型群2中的诊断价值最高(AUC=0.99;P<0.01),具有高特异性(95%)。与SARA显著增加一致(7.5vs10,P=0.021),双侧下CP,脊髓,随访期间脑桥被膜萎缩较多(P<0.05)。
结论:SCAs与HCs相比,幕下脑萎缩明显。我们确定了与幕下脑萎缩的实质性差异相关的两种不同的SCA表型群,临床表现,可能在某种程度上反映了潜在的分子分布,为更个性化的诊断和治疗方法铺平道路。
BACKGROUND: Clinical decision-making in spinocerebellar ataxia spectrum diseases (SCAs) has mainly been based on genetic tests, not considering the SCAs\' imaging and clinical heterogenicity.
OBJECTIVE: To identify SCAs phenogroups by analysis and hierarchical clustering of infratentorial morphological MRI for unveiling pathophysiological differences among common SCA subtypes.
METHODS: 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.
RESULTS: 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)n, 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).
CONCLUSIONS: 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.