Natural History of Vanishing White Matter
Natural History of Vanishing White Matter
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DOI：
10.1002/ana.25287
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发表时间：
2018-08-01
影响因子：
11.2
通讯作者：
van der Knaap, Marjo S.
中科院分区：
文献类型：
--
作者：
Hamilton, Eline M. C.;van der Lei, Hannemieke D. W.;van der Knaap, Marjo S.
目的全面描述消失白色物质（VWM）的自然史，旨在改善对患者/家属的咨询，并为今后的治疗试验提供自然史数据。通过疾病特异性临床问卷调查，健康效用指数和盖伊的神经功能障碍量表评估，和图表review.ResultsFirst疾病体征发生在中位年龄为3年（模式=2年，范围=出生前至54岁），60%的患者有症状的4岁之前。不同的发病年龄，第一个迹象的性质不同。总体而言，运动问题是最常见的表现，尤其是在儿童中。青少年和成人发病患者更有可能在疾病发作后早期表现出认知问题。102名患者死亡。多因素考克斯回归分析显示，发病年龄与保留截肢和生存率呈正相关。没有应激诱发的发作和癫痫发作的情况下预测更有利的结果。在4年前发病的患者中，早期发病与更严重的残疾和更高的死亡率相关。发病4年后，病程一般较轻，严重程度差异很大。性别或5个eIF 2B基因组之间无显著差异。结果证实了存在的基因型-表型correlation.InterpretationThe VWM疾病谱由一个连续的非常广泛的变异。发病年龄是病程的一个强有力的预测因素。神经学年鉴2018;84：274-288
ObjectiveTo comprehensively describe the natural history of vanishing white matter (VWM), aiming at improving counseling of patients/families and providing natural history data for future therapeutic trials.MethodsWe performed a longitudinal multicenter study among 296 genetically confirmed VWM patients. Clinical information was obtained via disease-specific clinical questionnaire, Health Utilities Index and Guy's Neurological Disability Scale assessments, and chart review.ResultsFirst disease signs occurred at a median age of 3 years (mode=2 years, range=before birth to 54 years); 60% of patients were symptomatic before the age of 4 years. The nature of the first signs varied for different ages of onset. Overall, motor problems were the most common presenting sign, especially in children. Adolescent and adult onset patients were more likely to exhibit cognitive problems early after disease onset. One hundred two patients were deceased. Multivariate Cox regression analysis revealed a positive relation between age at onset and both preservation of ambulation and survival. Absence of stress-provoked episodes and absence of seizures predicted more favorable outcome. In patients with onset before 4 years, earlier onset was associated with more severe disability and higher mortality. For onset from 4 years on, disease course was generally milder, with a wide variation in severity. There were no significant differences for sex or for the 5 eIF2B gene groups. The results confirm the presence of a genotype-phenotype correlation.InterpretationThe VWM disease spectrum consists of a continuum with extremely wide variability. Age at onset is a strong predictor for disease course. Ann Neurol 2018;84:274-288