Child Neurology and Psychiatry Section, Department of Clinical and Experimental Medicine, University of Catania, Policlinico, Via Santa Sofia 78, 95123, Catania, Italy.
Department "GF Ingrassia", Section of Neurosciences, University of Catania, Catania, Italy.
Cerebellum. 2021 Aug;20(4):596-605. doi: 10.1007/s12311-021-01242-x. Epub 2021 Feb 22.
We aimed to identify clinical, molecular and radiological correlates of activities of daily living (ADL) in patients with cerebellar atrophy caused by PMM2 mutations (PMM2-CDG), the most frequent congenital disorder of glycosylation. Twenty-six PMM2-CDG patients (12 males; mean age 13 ± 11.1 years) underwent a standardized assessment to measure ADL, ataxia (brief ataxia rating scale, BARS) and phenotype severity (Nijmegen CDG rating scale, NCRS). MRI biometry of the cerebellum and the brainstem were performed in 23 patients (11 males; aged 5 months-18 years) and 19 control subjects with equal gender and age distributions. The average total ADL score was 15.3 ± 8.5 (range 3-32 out of 36 indicating severe functional disability), representing variable functional outcome in PMM2-CDG patients. Total ADL scores were significantly correlated with NCRS (r = 0.55, p < 0.001) and BARS scores (r = 0.764; p < 0.001). Severe intellectual disability, peripheral neuropathy, and severe PMM2 variants were all significantly associated with worse functional outcome. Higher ADL scores were significantly associated with decreased diameters of cerebellar vermis (r = 0.347; p = 0.004), hemispheres (r = 0.436; p = 0.005), and brainstem, particularly the mid-pons (r = 0.64; p < 0.001) representing the major radiological predictor of functional disability score in multivariate regression analysis. We show that cerebellar syndrome severity, cognitive level, peripheral neuropathy, and genotype correlate with ADL used to quantify disease-related deficits in PMM2-CDG. Brainstem involvement should be regarded among functional outcome predictors in patients with cerebellar atrophy caused by PMM2-CDG.
我们旨在确定由 PMM2 突变引起的小脑萎缩（PMM2-CDG）患者日常生活活动（ADL）的临床、分子和影像学相关性，PMM2-CDG 是最常见的先天性糖基化障碍。26 名 PMM2-CDG 患者（12 名男性；平均年龄 13 ± 11.1 岁）接受了标准化评估，以测量 ADL、共济失调（简短共济失调评分量表，BARS）和表型严重程度（Nijmegen CDG 评分量表，NCRS）。23 名患者（11 名男性；年龄 5 个月至 18 岁）和 19 名性别和年龄分布均等的对照组进行了小脑和脑干的 MRI 生物测量。平均总 ADL 得分为 15.3 ± 8.5（36 分中的 3-32 分表示严重功能障碍），表明 PMM2-CDG 患者的功能结果存在差异。总 ADL 评分与 NCRS（r = 0.55，p < 0.001）和 BARS 评分（r = 0.764；p < 0.001）显著相关。严重智力残疾、周围神经病和严重的 PMM2 变异均与较差的功能结局显著相关。较高的 ADL 评分与小脑蚓部（r = 0.347；p = 0.004）、半球（r = 0.436；p = 0.005）和脑干，特别是中脑桥（r = 0.64；p < 0.001）的直径减小显著相关，这在多变量回归分析中是功能残疾评分的主要影像学预测因子。我们表明，小脑综合征严重程度、认知水平、周围神经病和基因型与用于量化 PMM2-CDG 相关疾病缺陷的 ADL 相关。在由 PMM2 引起的小脑萎缩患者中，脑干受累应被视为功能结局预测因素之一。
