Department of Paediatric Neurology/Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
Department of Neurology, OLVG Hospital, Amsterdam, The Netherlands.
Brain. 2019 Feb 1;142(2):334-343. doi: 10.1093/brain/awy299.
Males with adrenoleukodystrophy develop progressive myelopathy causing severe disability later in life. No treatment is currently available, but new disease-modifying therapies are under development. Knowledge of the natural history of the myelopathy is of paramount importance for evaluation of these therapies in clinical trials, but prospective data on disease progression are lacking. We performed a prospective observational cohort study to quantify disease progression over 2 years of follow-up. Signs and symptoms, functional outcome measures and patient-reported outcomes were assessed at baseline, 1 and 2 years of follow-up. We included 46 male adrenoleukodystrophy patients (median age 45.5 years, range 16-71). Frequency of myelopathy at baseline increased with age from 30.8% (<30 years) to 94.7% (>50 years). Disease progression was measured in the patients who were symptomatic at baseline (n = 24) or became symptomatic during follow-up (n = 1). Significant progression was detected with the functional outcome measures and quantitative vibration measurements. Over 2 years of follow-up, Expanded Disability Status Score increased by 0.34 points (P = 0.034), Severity Scoring system for Progressive Myelopathy decreased by 2.78 points (P = 0.013), timed up-and-go increased by 0.82 s (P = 0.032) and quantitative vibration measurement at the hallux decreased by 0.57 points (P = 0.040). Changes over 1-year follow-up were not significant, except for the 6-minute walk test that decreased by 19.67 meters over 1 year (P = 0.019). None of the patient-reported outcomes were able to detect disease progression. Our data show that progression of myelopathy in adrenoleukodystrophy can be quantified using practical and clinically relevant outcome measures. These results will help in the design of clinical trials and the development of new biomarkers for the myelopathy of adrenoleukodystrophy.10.1093/brain/awy299_video1awy299media15995811923001.
男性肾上腺脑白质营养不良会发展为进行性脊髓病，导致生命后期严重残疾。目前尚无治疗方法，但新的疾病修饰疗法正在开发中。了解脊髓病的自然史对于评估这些疗法在临床试验中的效果至关重要，但缺乏疾病进展的前瞻性数据。我们进行了一项前瞻性观察队列研究，以量化 2 年随访期间的疾病进展。在基线、1 年和 2 年随访时评估体征和症状、功能结局测量和患者报告的结局。我们纳入了 46 名男性肾上腺脑白质营养不良患者（中位年龄 45.5 岁，范围 16-71 岁）。基线时脊髓病的频率随年龄增加而增加，从 30.8%（<30 岁）增加到 94.7%（>50 岁）。在基线时有症状的患者（n=24）或在随访期间出现症状的患者（n=1）中测量疾病进展。功能结局测量和定量振动测量检测到显著进展。在 2 年的随访中，扩展残疾状况评分增加了 0.34 分（P=0.034），进展性脊髓病严重程度评分系统降低了 2.78 分（P=0.013），计时起立行走试验增加了 0.82 秒（P=0.032），大脚趾定量振动测量降低了 0.57 分（P=0.040）。除了 1 年时 6 分钟步行测试减少了 19.67 米（P=0.019）外，1 年随访的变化不显著。患者报告的结局均无法检测到疾病进展。我们的数据表明，使用实用且具有临床相关性的结局测量方法可以定量评估肾上腺脑白质营养不良脊髓病的进展。这些结果将有助于设计临床试验和开发新的肾上腺脑白质营养不良脊髓病生物标志物。
