Histologic muscular history in steroid-treated and untreated patients with Duchenne dystrophy
Histologic muscular history in steroid-treated and untreated patients with Duchenne dystrophy
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DOI：
10.1212/wnl.0000000000002147
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发表时间：
2015-11-24
期刊：
影响因子：
9.9
通讯作者：
Moggio, Maurizio
中科院分区：
文献类型：
--
作者：
Peverelli, Lorenzo;Testolin, Silvia;Moggio, Maurizio
目的：杜氏肌营养不良症（DMD）是一种致死性疾病。在许多治疗试验中使用的结局指标包括骨骼肌活检。我们研究了DMD的自然历史，从肌肉组织学的角度来看，目的是提供一个可重复的工具，用于评估和比较任何组织学变化发生在DMD患者接受治疗，因此能够确定如何治疗调制的组织学演变的diseases.Methods：三个独立的运营商分析了56个肌肉活检40例未接受类固醇治疗，年龄1至10岁，16个人接受类固醇治疗，年龄7至10岁。我们分析了形态学的措施，规范化的每一个措施的平均数量的纤维观察到的每一年的年龄，并计算intraclasscorrelation coefficients.Results：平均比例的结缔组织在未接受类固醇治疗的患者为16.98%，从年龄1至6岁和30%，从年龄7至10岁（p < 0.0001）。使用激素治疗的患者平均比例为24.90%。肌纤维面积反映了结缔组织在这两个group.Conclusions：提供了一个可重复的工具进行临床试验的患者发生的组织学变化的评价和比较，据观察，在6至7岁，纤维化组织迅速达到峰值29.85%，这是一个关键时刻，肌肉组织失去了自我再生能力，转向纤维化变性。在决定最合适的开始治疗时间时，应考虑这些数据。
Objective:Duchenne muscular dystrophy (DMD) is a lethal disease. The outcome measures used in numerous therapeutic trials include skeletal muscle biopsy. We studied the natural history of DMD from the standpoint of muscle histology with the aim of providing a reproducible tool for use in evaluating and comparing any histologic changes occurring in patients with DMD undergoing treatment and hence be able to determine how therapy modulates the histologic evolution of the disease.Methods:Three independent operators analyzed 56 muscle biopsies from 40 patients not treated with steroids, aged 1 to 10 years and 16 individuals treated with steroids, aged 7 to 10 years. We analyzed morphologic measures, normalized every measure for the average number of fibers observed for each year of age, and calculated intraclass correlation coefficients.Results:The average proportion of connective tissue in patients not treated with steroids was 16.98% from ages 1 to 6 years and 30% from ages 7 to 10 years (p < 0.0001). The average proportion in patients treated with steroids was 24.90%. Muscle fiber area mirrored that of connective tissue in both groups.Conclusions:Having provided a reproducible tool for evaluation and comparison of histologic changes occurring in patients undergoing clinical trials, it was observed that at ages 6 to 7 years, fibrotic tissue rapidly peaks to 29.85%; this is a crucial moment when muscle tissue loses its self-regeneration ability, veering toward fibrotic degeneration. These data should be considered when deciding the most suitable time to begin therapy.