典型婴儿庞贝氏症患者的长期存活率显示出大脑进行性异常和认知功能变化的谱系

IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM
J. J. A. van den Dorpel, M. J. Mackenbach, M. H. G. Dremmen, W. M. C. van der Vlugt, D. Rizopoulos, P. A. van Doorn, A. T. van der Ploeg, R. Muetzel, N. A. M. E. van der Beek, J. M. P. van den Hout
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引用次数: 0

摘要

这项纵向队列研究旨在进一步了解典型婴儿型庞贝病患者大脑异常的模式以及可能对认知功能造成的影响。我们纳入了 19 名接受 ERT 治疗的典型婴儿庞贝病患者(最后一次评估的中位年龄为 8.9 岁,范围为 1.5-22.5 岁;5/19 CRIM 阴性)。通过脑部磁共振成像(T1、T2 和 FLAIR 采集),我们在随访的多个时间点对脑部异常的进展情况进行了 12 级评分。此外,我们还注意到了特定的白质模式并检查了萎缩情况。认知能力的发展是通过认证神经心理学家进行的韦氏智商评估来研究的。年龄与认知功能、核磁共振成像评分与认知功能之间的关系通过线性回归模型进行评估。除一名患者外,所有患者都出现了脑部异常。整个大脑的异常发展模式相似,早期累及脑室周围白质,随后累及皮层下白质、灰质结构和并皮层U纤维。我们发现,随着年龄的增长,全量表智商、表现智商和处理速度会明显下降(p <0.01),但言语智商不会下降(p = 0.17)。磁共振成像 12 分评分表每增加一分,所有智商指数得分都会显著下降(3.1-6.0 分)(p < 0.05)。在我们的队列中,大多数长期存活的患者会出现脑磁共振成像增量异常和认知功能下降。这突显了我们需要能够穿越血脑屏障的新疗法来治疗这种中枢神经系统表型。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Long term survival in patients with classic infantile Pompe disease reveals a spectrum with progressive brain abnormalities and changes in cognitive functioning

Long term survival in patients with classic infantile Pompe disease reveals a spectrum with progressive brain abnormalities and changes in cognitive functioning

The aim of this longitudinal cohort study, is to provide more insight into the pattern of brain abnormalities, and possible consequences for cognitive functioning, in patients with classic infantile Pompe disease. We included 19 classic infantile Pompe patients (median age last assessment 8.9 years, range 1.5–22.5 years; 5/19 CRIM negative), treated with ERT. Using MR imaging of the brain (T1, T2, and FLAIR acquisitions), we classified progression of brain abnormalities on a 12-point rating scale at multiple time points throughout follow-up. Additionally we noted specific white matter patterns and examined atrophy. Cognitive development was studied using Wechsler IQ assessments obtained by certified neuropsychologists. The association between age and cognitive functioning, and MRI ratings and cognitive functioning was assessed by linear regression models. All but one patient developed brain abnormalities. The abnormalities progressed in a similar pattern throughout the brain, with early involvement of periventricular white matter, later followed by subcortical white matter, gray matter structures, and juxtacortical U-fibers. We found a significant decline (p < 0.01), with increasing age for full scale IQ, performance IQ and processing speed, but not for verbal IQ (p = 0.17). Each point increment in the 12-point MRI rating scale was associated with a significant decline (3.1–6.0 points) in all the IQ index scores (p < 0.05). The majority of long-term surviving patients in our cohort develop incremental brain MRI abnormalities and decline in cognitive functioning. This highlights the need for new therapies that can cross the blood–brain barrier in order to treat this CNS phenotype.

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来源期刊
Journal of Inherited Metabolic Disease
Journal of Inherited Metabolic Disease 医学-内分泌学与代谢
CiteScore
9.50
自引率
7.10%
发文量
117
审稿时长
4-8 weeks
期刊介绍: The Journal of Inherited Metabolic Disease (JIMD) is the official journal of the Society for the Study of Inborn Errors of Metabolism (SSIEM). By enhancing communication between workers in the field throughout the world, the JIMD aims to improve the management and understanding of inherited metabolic disorders. It publishes results of original research and new or important observations pertaining to any aspect of inherited metabolic disease in humans and higher animals. This includes clinical (medical, dental and veterinary), biochemical, genetic (including cytogenetic, molecular and population genetic), experimental (including cell biological), methodological, theoretical, epidemiological, ethical and counselling aspects. The JIMD also reviews important new developments or controversial issues relating to metabolic disorders and publishes reviews and short reports arising from the Society''s annual symposia. A distinction is made between peer-reviewed scientific material that is selected because of its significance for other professionals in the field and non-peer- reviewed material that aims to be important, controversial, interesting or entertaining (“Extras”).
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