Groulx-Boivin Emilie, Oliveira-Carneiro Andrea, Carlson Helen, Floer Amalia, Kirton Adam, Mah Jean, Saint-Martin Christine, La Piana Roberta, Oskoui Maryam
From the Departments of Pediatrics and Neurology and Neurosurgery (E.G.-B., M.O.), Montreal Children's Hospital, McGill University; Research Institute (A.O.-C., M.O.), McGill University Health Centre, Montreal, Quebec; Alberta Children's Hospital Research Institute (H.C., A.F., A.K., J.M.); Department of Pediatrics (H.C., A.F., A.K., J.M.), Cumming School of Medicine, University of Calgary, Alberta; Division of Pediatric Medical Imaging (C.S.-M.), Department of Radiology, Montreal Children's Hospital; Department of Neurology and Neurosurgery (R.L.P.), Montreal Neurological Institute; and Department of Diagnostic Radiology (R.L.P.), McGill University, Montreal, Quebec, Canada.
Neurol Genet. 2024 Sep 20;10(5):e200193. doi: 10.1212/NXG.0000000000200193. eCollection 2024 Oct.
Most individuals with spinal muscular atrophy (SMA) on disease-modifying therapies continue to have chronic motor impairment. Insights into brain involvement in SMA may open new pathways for adjunctive therapies to optimize outcomes. We aimed to characterize macrostructural brain abnormalities detected by MRI in individuals with SMA compared with peer controls.
We conducted a cross-sectional case-control study of children and adults with a confirmed genetic diagnosis of 5q SMA, and peer controls matched by age and sex. Brain MRIs acquired on a 3T MRI scanner through a standardized research protocol were reviewed to qualitatively assess the presence of macrostructural changes. The primary outcome was the presence of any structural brain anomaly on MRI. In addition, the total volume of each participant's lateral ventricles was quantified by volumetry using MRIcron. Genetic and clinical variables, including copy number and motor function (Hammersmith Functional Motor Scale Expanded and Revised Upper Limb Module scores), were then correlated with neuroimaging findings.
A total of 42 participants completed the study (mean age 17.4, range 7-40; 67% male). Of the 21 individuals with 5q SMA, 9 (43%) had macrostructural brain abnormalities identified on MRI compared with 2 of 21 (10%) peer controls (odds ratio 7.1, 95% confidence interval 1.4-34.0). In patients with SMA, the most common structural changes were widening of the arachnoid spaces (n = 4) and ventriculomegaly (n = 4). Individuals with SMA had larger median lateral ventricular volume than their normally developing peers (9.3 mL, interquartile range [IQR] 5.5-13.1 vs 5.3 mL, IQR 3.8-9.8; = 0.034). Structural brain abnormalities were more frequent in those with 2 copies (3/5, 60%) compared with 3 or 4 copies (4/10, 40% and 2/6, 33% respectively), not reaching significance. We found no association between structural changes and motor function scores.
Individuals with SMA have higher rates of macrostructural brain abnormalities than their neurotypical peers, suggesting CNS involvement in SMA. Understanding changes in the brain architecture of the SMA population can inform the development of adjunct therapies targeting the CNS and potentially guide rehabilitation strategies.
大多数接受疾病修饰疗法的脊髓性肌萎缩症（SMA）患者仍存在慢性运动障碍。深入了解SMA患者大脑受累情况可能为辅助治疗开辟新途径，以优化治疗效果。我们旨在描述与同龄对照相比，SMA患者通过MRI检测到的大脑宏观结构异常。
我们对确诊为5q SMA的儿童和成人以及按年龄和性别匹配的同龄对照进行了一项横断面病例对照研究。回顾通过标准化研究方案在3T MRI扫描仪上获取的脑部MRI，以定性评估宏观结构变化的存在情况。主要结局是MRI上是否存在任何大脑结构异常。此外，使用MRIcron通过容积测量法对每位参与者侧脑室的总体积进行量化。然后将遗传和临床变量，包括拷贝数和运动功能（哈默史密斯功能运动量表扩展版和修订版上肢模块评分）与神经影像学结果进行关联。
共有42名参与者完成了研究（平均年龄17.4岁，范围7 - 40岁；67%为男性）。在21名5q SMA患者中，9名（43%）在MRI上发现有大脑宏观结构异常，而21名同龄对照中有2名（10%）出现异常（比值比7.1，95%置信区间1.4 - 34.0）。在SMA患者中，最常见的结构变化是蛛网膜下腔增宽（n = 4）和脑室扩大（n = 4）。SMA患者的侧脑室中位数体积大于正常发育的同龄人（9.3 mL，四分位间距[IQR] 5.5 - 13.1 vs 5.3 mL，IQR 3.8 - 9.8；P = 0.034）。与有3或4个拷贝的患者（分别为4/10，40%和2/6，33%）相比，有2个拷贝的患者大脑结构异常更常见（3/5，60%），但未达到显著差异。我们发现结构变化与运动功能评分之间无关联。
SMA患者大脑宏观结构异常的发生率高于神经典型的同龄人，提示中枢神经系统受累于SMA。了解SMA人群大脑结构的变化可为针对中枢神经系统的辅助治疗开发提供信息，并可能指导康复策略。
