Volume of Gadolinium Enhancement and Successful Repair of the Blood-Brain Barrier in Cerebral Adrenoleukodystrophy

IF 4.3 Q1 Medicine
Troy C. Lund , Michelle Ng , Paul J. Orchard , Daniel J. Loes , Gerald V. Raymond , Ashish Gupta , Dan Kenny-Jung , David R. Nascene
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引用次数: 4

Abstract

Up to 40% of boys with adrenoleukodystrophy develop a severe central nervous system demyelinating form (cALD) characterized by white matter changes and gadolinium enhancement on magnetic resonance imaging (MRI). Hematopoietic cell transplant (HCT) is the only proven means to attenuate cALD progression. The elimination of active neuroinflammation is indicated radiographically by the resolution of gadolinium (Gd) enhancement and correlates to speed of donor neutrophil recovery. We analyzed 66 boys with cALD undergoing HCT for biomarkers correlating with early (30 days post-HCT) Gd signal resolution. We found that log Gd volume (cm3) on pre-HCT MRI strongly positively correlated to day 30 Gd resolution (P = .0003) with smaller volume correlating to higher proportion resolved, as was the baseline gadolinium intensity score (P = .04), plasma chitotriosidase activity (P = .04), and faster absolute neutrophil count recovery (P = .03). In multivariate analysis, log Gd volume remained superior in determining which patients would have Gd signal resolution by 30 days post-HCT (P = .016). A final analysis indicated that early Gd resolution also correlated with less neurologic progression from baseline to 1 year following HCT (P = .006). MRI Gd volume may serve as a contributing biomarker to better delineate outcomes and an important metric in comparing therapies in the treatment of cALD.

脑肾上腺白质营养不良患者的钆增强体积和血脑屏障的成功修复
高达40%的肾上腺脑白质营养不良男孩发展为严重的中枢神经系统脱髓鞘形式(cALD),其特征是白质改变和磁共振成像(MRI)的钆增强。造血细胞移植(HCT)是唯一被证实的减轻cALD进展的方法。活动性神经炎症的消除是通过钆(Gd)增强的分辨率来指示的,并与供体中性粒细胞恢复的速度相关。我们分析了66名接受HCT的cALD男孩,以寻找与早期(HCT后30天)Gd信号分辨率相关的生物标志物。我们发现,hct前MRI上的Gd体积(cm3)与第30天的Gd分辨率呈强正相关(P = 0.0003),体积越小,分辨率越高,基线钆强度评分(P = .04)、血浆壳三酸苷酶活性(P = .04)和绝对中性粒细胞计数恢复速度越快(P = .03)也是如此。在多变量分析中,对数Gd体积在确定hct后30天Gd信号分辨率方面仍然优于其他患者(P = .016)。最终分析表明,早期Gd消退也与HCT后基线至1年的神经系统进展较少相关(P = .006)。MRI Gd体积可以作为一种有贡献的生物标志物,以更好地描述结果,并作为比较cALD治疗方法的重要指标。
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来源期刊
CiteScore
6.60
自引率
0.00%
发文量
1061
审稿时长
3-6 weeks
期刊介绍: Biology of Blood and Marrow Transplantation publishes original research reports, reviews, editorials, commentaries, letters to the editor, and hypotheses and is the official publication of the American Society for Transplantation and Cellular Therapy. The journal focuses on current technology and knowledge in the interdisciplinary field of hematopoetic stem cell transplantation.
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