Natural history of pulmonary function in collagen VI-related myopathies
Natural history of pulmonary function in collagen VI-related myopathies
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DOI：
10.1093/brain/awt284
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发表时间：
2013-12-01
期刊：
影响因子：
14.5
通讯作者：
Boennemann, Carsten G.
中科院分区：
文献类型：
--
作者：
Foley, A. Reghan;Quijano-Roy, Susana;Boennemann, Carsten G.
与肌肉细胞外基质中VI型胶原缺乏或功能障碍相关的临床表型谱统称为“VI型胶原相关肌病”，包括乌尔里希先天性肌营养不良症、Bethlem肌病和中间表型。为了进一步确定这些变异的临床过程，我们通过分析大型国际队列中的纵向强迫肺活量数据，研究了与vi型胶原相关肌病中运动能力相关的肺功能自然史。在美国（n = 2）、英国（n = 2）、澳大利亚（n = 2）、意大利（n = 2）、法国（n = 1）和比利时（n = 1） 10个神经肌肉中心对遗传和/或病理证实的vi型胶原相关肌病患者进行回顾性图表回顾。145例患者的486项强制肺活量测量结果可供分析。符合乌尔里希先天性肌营养不良症原始描述的临床谱严重端患者很容易通过严重的肌肉无力来识别，这些肌肉无力可以阻止行走或导致早期行走能力丧失，并且每年强制肺活量累计下降2.6% （P < 0.0001）。功能能力较好的患者，在有/没有辅助的情况下行走，最初合并，在一组中包含中间和Bethlem肌病表型。然而，一组患者表现出肺功能持续下降，而另一组患者肺功能稳定。肺功能下降的患者无跳跃或奔跑能力；这些患者被归类为中度vi型胶原相关肌病，其余患者被归类为Bethlem肌病。中级患者的强迫肺活量每年累计下降2.3% (P < 0.0001)，而Bethlem肌病患者的年龄与强迫肺活量之间的关系不显著（P = 0.1432）。乌尔里希先天性肌营养不良患者开始夜间无创通气的时间为11.3年（+/- 4.0），中度vi型胶原相关肌病患者为20.7年（+/- 1.5）。最大运动能力与用力肺活量的关系极显著（P < 0.0001）。这项研究表明，肺功能谱可以与运动功能谱结合使用，对vi型胶原相关肌病患者进行表型分层。这些发现提高了我们对胶原vi相关肌病的自然史的认识，使护理的主动优化和为临床试验的患者群体做好准备。
The spectrum of clinical phenotypes associated with a deficiency or dysfunction of collagen VI in the extracellular matrix of muscle are collectively termed 'collagen VI-related myopathies' and include Ullrich congenital muscular dystrophy, Bethlem myopathy and intermediate phenotypes. To further define the clinical course of these variants, we studied the natural history of pulmonary function in correlation to motor abilities in the collagen VI-related myopathies by analysing longitudinal forced vital capacity data in a large international cohort. Retrospective chart reviews of genetically and/or pathologically confirmed collagen VI-related myopathy patients were performed at 10 neuromuscular centres: USA (n = 2), UK (n = 2), Australia (n = 2), Italy (n = 2), France (n = 1) and Belgium (n = 1). A total of 486 forced vital capacity measurements obtained in 145 patients were available for analysis. Patients at the severe end of the clinical spectrum, conforming to the original description of Ullrich congenital muscular dystrophy were easily identified by severe muscle weakness either preventing ambulation or resulting in an early loss of ambulation, and demonstrated a cumulative decline in forced vital capacity of 2.6% per year (P < 0.0001). Patients with better functional abilities, in whom walking with/without assistance was achieved, were initially combined, containing both intermediate and Bethlem myopathy phenotypes in one group. However, one subset of patients demonstrated a continuous decline in pulmonary function whereas the other had stable pulmonary function. None of the patients with declining pulmonary function attained the ability to hop or run; these patients were categorized as intermediate collagen VI-related myopathy and the remaining patients as Bethlem myopathy. Intermediate patients had a cumulative decline in forced vital capacity of 2.3% per year (P < 0.0001) whereas the relationship between age and forced vital capacity in patients with Bethlem myopathy was not significant (P = 0.1432). Nocturnal non-invasive ventilation was initiated in patients with Ullrich congenital muscular dystrophy by 11.3 years (+/- 4.0) and in patients with intermediate collagen VI-related myopathy by 20.7 years (+/- 1.5). The relationship between maximal motor ability and forced vital capacity was highly significant (P < 0.0001). This study demonstrates that pulmonary function profiles can be used in combination with motor function profiles to stratify collagen VI-related myopathy patients phenotypically. These findings improve our knowledge of the natural history of the collagen VI-related myopathies, enabling proactive optimization of care and preparing this patient population for clinical trials.