From the Department of Pediatrics (E.J.M., A.T.), Division of Child Neurology, Weill Cornell Medical College, New York-Presbyterian Hospital; Department of Pediatrics (E.J.M.), Memorial Sloan Kettering Cancer Center, New York, NY; Department of Neurology (K.P.V.H.), Stanford University Schoolds of Medicine, Lucile Packard Children's Hospital, CA; Department of Pediatric Neurology, Emma Children's Hospital, Amsterdam University Medical Centers, the Netherlands; Department of Genetic Medicine (G.V.R.), Johns Hopkins University, Baltimore, MD; The Moser Center for Leukodystrophies (A.F.), Kennedy Krieger Institute, Johns Hopkins University, Baltimore, MD; and Department of Neurology (F.S.E.), Harvard Medical School, Massachusetts General Hospital, Boston.
Neurology. 2022 Aug 1;99(5):e512-e520. doi: 10.1212/WNL.0000000000200571.
We sought to characterize the natural history and standard-of-care practices between the radiologic appearance of brain lesions, the appearance of lesional enhancement, and treatment with hematopoietic stem-cell transplant or gene therapy among boys diagnosed with presymptomatic childhood-onset cerebral adrenoleukodystrophy (CCALD).
We analyzed a multicenter, mixed retrospective/prospective cohort of patients diagnosed with presymptomatic CCALD (Neurologic Function Score = 0, Loes Score [LS] = 0.5-9.0, and age <13 years). Two time-to-event survival analyses were conducted: (1) time from CCALD lesion onset-to-lesional enhancement and (2) time from enhancement-to-treatment. The analysis was repeated in the subset of patients with (1) the earliest evidence of CCALD, defined as an MRI LS ≤ 1, and (2) patients diagnosed between 2016 and 2021.
Seventy-one boys were diagnosed with presymptomatic cerebral lesions at a median age of 6.4 years [2.4-12.1] with a LS of 1.5 [0.5-9.0]. Fifty percent of patients had lesional enhancement at diagnosis. In the remaining 50%, the median Kaplan-Meier (KM)-estimate of time from diagnosis-to-lesional enhancement was 6.0 months (95% CI 3.6-17.8). The median KM-estimate of time from enhancement-to-treatment is 3.8 months (95% CI 2.8-5.9); 2 patients (4.2%) developed symptoms before treatment. Patients with a diagnostic LS ≤ 1 were younger (5.8 years [2.4-11.5]), had a time-to-enhancement of 4.7 months (95% CI 2.7-9.30), and were treated in 3.8 months (95% CI 3.1-7.1); no patients developed symptoms before treatment. Time from CCALD diagnosis-to-treatment decreased over the course of the study (ρ = -0.401, = 0.003).
Our findings offer a more refined understanding of the timing of lesion formation, enhancement, and treatment among boys with presymptomatic CCALD. These data offer benchmarks for standardizing clinical care and designing future clinical trials.
我们旨在描述脑病变的放射学表现、病变增强的出现，以及接受造血干细胞移植或基因治疗之间的自然病史和标准治疗实践，这些是在诊断为儿童起病脑肾上腺脑白质营养不良（CCALD）的无症状男孩中。
我们分析了一个多中心、混合回顾性/前瞻性队列的患者，这些患者被诊断为无症状 CCALD（神经功能评分=0，Loes 评分[LS] = 0.5-9.0，年龄<13 岁）。进行了两次时间事件生存分析：（1）CCALD 病变发病到病变增强的时间；（2）增强到治疗的时间。在以下亚组中重复了该分析：（1）最早的 CCALD 证据，定义为 MRI LS ≤ 1；（2）2016 年至 2021 年诊断的患者。
71 名男孩在中位年龄为 6.4 岁[2.4-12.1]时被诊断为无症状脑病变，LS 为 1.5[0.5-9.0]。50%的患者在诊断时存在病变增强。在其余的 50%患者中，中位 Kaplan-Meier（KM）估计从诊断到病变增强的时间为 6.0 个月（95%CI 3.6-17.8）。从增强到治疗的中位 KM 估计时间为 3.8 个月（95%CI 2.8-5.9）；2 名患者（4.2%）在治疗前出现症状。LS ≤ 1 的诊断患者年龄更小（5.8 岁[2.4-11.5]），增强时间为 4.7 个月（95%CI 2.7-9.30），治疗时间为 3.8 个月（95%CI 3.1-7.1）；无患者在治疗前出现症状。随着研究的进行，从 CCALD 诊断到治疗的时间减少（ρ=-0.401， =0.003）。
我们的研究结果提供了对无症状 CCALD 男孩中病变形成、增强和治疗时间的更深入了解。这些数据为标准化临床护理和设计未来临床试验提供了基准。
