Glemser Philip A, Jaeger Heike, Nagel Armin M, Ziegler Andreas E, Simons David, Schlemmer Heinz-Peter, Lehmann-Horn Frank, Jurkat-Rott Karin, Weber Marc-André
Department of Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Institute of Forensic Medicine, University of Heidelberg, Heidelberg, Germany.
Acta Myol. 2017 Mar;36(1):2-13.
In this pilot study we tested whether a low dose application of a mild diuretic substance such as eplerenone is beneficial in early stages of Duchenne muscular dystrophy using Na und H imaging, myometry, and clinical testing versus the glucocorticoid gold standard. Two 7-years old patients with DMD were examined on a 3T MRI system. H MRI and Na density-adapted 3-dimensional radial MRI sequences were performed both before and 1, 3 and 6 months after therapy with eplerenone respectively cortisone. We quantified fatty infiltration on T1-weighted images using subcutaneous fat as reference and fat fraction with a two-point DIXON sequence. Muscle oedema was quantified on STIR images and DIXON water maps with background noise as reference. We quantified Na by a muscular tissue concentration sequence with a 51.3mM Na with 5% agarose reference tube. A Na IR-sequence was used for determination of mainly myoplasmic Na. Correspondingly myometry of muscles and tendons were assessed. Clinical tests (i.e. 4-steps-test) and blood counts (i.e. K) were done by a pediatrician. Under eplerenone therapy we detected a reduction of muscular oedema, intracellular-weighted sodium IR signal and muscular sodium concentration. The oedema reduction in the DMD patient receiving eplerenone was more pronounced to the patient with cortisone. Myometric-measured tissue parameters such as muscle stiffness had a more pronounced effect in the child treated with eplerenone after a first increase in muscle stiffness both after eplerenone and cortisone treatment. Clinical abilities during both therapies were mostly constant. Eplerenone might be a possible new therapy option in DMD patients.
在这项试点研究中,我们使用钠和氢成像、肌动测量法以及临床测试,对比糖皮质激素这一黄金标准,测试了低剂量应用轻度利尿剂依普利酮在杜兴氏肌营养不良症早期是否有益。两名7岁的杜兴氏肌营养不良症患者在3T磁共振成像(MRI)系统上接受了检查。分别在使用依普利酮和可的松治疗前以及治疗后1、3和6个月,进行了氢MRI和钠密度适配的三维径向MRI序列检查。我们以皮下脂肪为参照,通过T1加权图像量化脂肪浸润,并使用两点DIXON序列量化脂肪分数。以背景噪声为参照,在短TI反转恢复(STIR)图像和DIXON水图上量化肌肉水肿。我们通过一个含51.3mM钠的肌肉组织浓度序列和5%琼脂糖参比管来量化钠。一个钠反转恢复(IR)序列用于主要测定肌浆内的钠。相应地,对肌肉和肌腱进行了肌动测量评估。临床测试(即四步测试)和血常规检查(即血钾)由一名儿科医生完成。在依普利酮治疗下,我们检测到肌肉水肿、细胞内加权钠IR信号和肌肉钠浓度降低。接受依普利酮治疗的杜兴氏肌营养不良症患者的水肿减轻比接受可的松治疗的患者更明显。在依普利酮和可的松治疗后肌肉僵硬均先增加的情况下,肌动测量所测的组织参数(如肌肉僵硬度)在接受依普利酮治疗的儿童中影响更为显著。两种治疗期间的临床能力大多保持不变。依普利酮可能是杜兴氏肌营养不良症患者一种新的潜在治疗选择。