Development of a neurologic severity scale for Aicardi Goutieres Syndrome
Development of a neurologic severity scale for Aicardi Goutieres Syndrome
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DOI：
10.1016/j.ymgme.2020.03.008
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发表时间：
2020-06-01
影响因子：
3.8
通讯作者：
Vanderver, Adeline
中科院分区：
文献类型：
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作者：
Adang, Laura A.;Gavazzi, Francesco;Vanderver, Adeline
背景和目的：Aicardi Goutieres 综合征（AGS）是一种严重的自身炎症性脑白质营养不良，其特征是全身神经功能障碍。我们的目标是创建一个易于应用的量表，与 AGS 相关的独特发展挑战相关。方法：所有个体都是通过我们的自然历史研究招募的。根据 AGS 严重程度将个体分为轻度、中度或重度，并根据三个功能分类量表的总和计算临床遇到的神经功能综合评分。通过专家共识，我们确定了 11 个关键项目来反映 AGS 在粗大运动、精细运动和认知技能方面的严重程度，从而创建了 AGS 量表。具有很强的人际可靠性。 AGS 量表适用于现有的医疗记录，以评估一段时间内的神经功能。将 AGS 量表与粗大运动功能标准测量（粗大运动功能测量-88、GMFM-88）和假定的疾病诊断生物标志物干扰素信号基因表达评分 (ISG) 的表现进行比较。结果：AGS 量表评分与严重程度分类和综合神经功能评分相关。当回顾性地应用到我们的自然历史研究中时，大多数人表现出功能最初下降，随后分数稳定。在疾病的前 6 个月内，AGS 评分是最动态的。 AGS 量表与 GMFM-88 的表现相关，但与 ISG 水平不相关。结论：本研究证明了 AGS 量表作为评估 AGS 神经功能的多模式工具的实用性。 AGS 量表与临床严重程度以及劳动密集型工具 GMFM-88 相关。这项研究强调了 ISG 评分作为疾病严重程度标志的局限性。通过 AGS 量表，我们发现 AGS 神经系统严重程度在疾病早期最为动态。这种新颖的 AGS 量表是一种很有前途的工具，可以纵向追踪这个独特人群的神经功能。
Background and purpose: Aicardi Goutieres Syndrome (AGS) is a severe, autoinflammatory leukodystrophy characterized by global neurologic dysfunction. Our goal was to create an easy-to-apply scale relevant to the unique developmental challenges associated with AGS.Methods: All individuals were recruited through our natural history study. Individuals were classified by AGS severity as mild, moderate, or severe, and clinical encounters were assigned a composite score for neurologic function calculated from the sum of three functional classification scales. Through expert consensus, we identified 11 key items to reflect the severity of AGS across gross motor, fine motor, and cognitive skills to create the AGS Scale. There was strong interrater reliability. The AGS scale was applied across available medical records to evaluate neurologic function over time. The AGS scale was compared to performance on a standard measure of gross motor function (Gross Motor Function Measure-88, GMFM-88) and a putative diagnostic biomarker of disease, the interferon signaling gene expression score (ISG).Results: The AGS scale score correlated with severity classifications and the composite neurologic function scores. When retrospectively applied across our natural history study, the majority of individuals demonstrated an initial decline in function followed by stable scores. Within the first 6 months of disease, the AGS score was the most dynamic. The AGS scale correlated with performance by the GMFM-88, but did not correlate with ISG levels.Conclusions: This study demonstrates the utility of the AGS scale as a multimodal tool for the assessment of neurologic function in AGS. The AGS scale correlates with clinical severity and with a more labor-intensive tool, GMFM-88. This study underscores the limitations of the ISG score as a marker of disease severity. With the AGS scale, we found that AGS neurologic severity is the most dynamic early in disease. This novel AGS scale is a promising tool to longitudinally follow neurologic function in this unique population.