Longitudinal volumetric analysis of gray matter atrophy in metachromatic leukodystrophy

IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Murtadha L. Al-Saady, Hristina Galabova, Daphne H. Schoenmakers, Shanice Beerepoot, Caroline Lindemans, Peter M. van Hasselt, Marjo S. van der Knaap, Nicole I. Wolf, Petra J. W. Pouwels
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Abstract

Metachromatic leukodystrophy (MLD) is an inherited lysosomal storage disorder characterized by arylsulfatase A (ASA) deficiency, leading to sulfatide accumulation and myelin degeneration in the central nervous system. While primarily considered a white matter (WM) disease, gray matter (GM) is also affected in MLD, and hematopoietic stem cell transplantation (HSCT) may have limited effect on GM atrophy. We cross-sectionally and longitudinally studied GM volumes using volumetric MRI in a cohort of 36 (late-infantile, juvenile and adult type) MLD patients containing untreated and HSCT treated subjects. Cerebrum, cortical GM, (total) CSF, cerebellum, deep gray matter (DGM) (excluding thalamus) and thalamus volumes were analyzed. Longitudinal correlations with measures of cognitive and motor functioning were assessed. Cross-sectionally, juvenile and adult type patients (infantiles excluded based on limited numbers) were compared with controls at earliest scan, before possible treatment. Patients had lower cerebrum, cortical GM, DGM and thalamus volumes. Differences were most pronounced for adult type patients. Longitudinal analyses showed substantial and progressive atrophy of all regions and increase of CSF in untreated patients. Similar, albeit less pronounced, effects were seen in treated patients for cerebrum, cortical GM, CSF and thalamus volumes. Deterioration in motor performance (all patients) was related to atrophy, and increase of CSF, in all regions. Cognitive functioning (data available for treated patients) was related to cerebral, cortical GM and thalamus atrophy; and to CSF increase. Our findings illustrate the importance of recognizing GM pathology as a potentially substantial, clinically relevant part of MLD, apparently less amenable to treatment.

Abstract Image

变色性白质营养不良症灰质萎缩的纵向容积分析。
变色性白质营养不良症(MLD)是一种遗传性溶酶体储积症,其特征是丙烯基硫酸酯酶A(ASA)缺乏,导致硫化物蓄积和中枢神经系统髓鞘变性。虽然MLD主要被认为是一种白质(WM)疾病,但灰质(GM)也会受到影响,造血干细胞移植(HSCT)对GM萎缩的影响可能有限。我们使用容积核磁共振成像技术对36名(晚期畸形、幼年型和成年型)MLD患者(包括未接受治疗和造血干细胞移植治疗的受试者)进行了横截面和纵向的GM体积研究。研究分析了大脑、皮质GM、(总)CSF、小脑、深部灰质(DGM)(不包括丘脑)和丘脑的体积。评估了与认知和运动功能测量的纵向相关性。横向比较了青少年和成人型患者(由于人数有限,不包括婴儿)与可能接受治疗前最早扫描的对照组。患者的大脑、皮质GM、DGM和丘脑体积较小。成年型患者的差异最为明显。纵向分析表明,未经治疗的患者所有区域都出现了严重的进行性萎缩,脑脊液也有所增加。在接受治疗的患者中,大脑、皮质GM、CSF和丘脑体积也有类似的影响,但不太明显。运动能力的下降(所有患者)与所有区域的萎缩和 CSF 的增加有关。认知功能(治疗患者的可用数据)与大脑、皮层 GM 和丘脑萎缩以及 CSF 增加有关。我们的研究结果表明,认识到GM病理学是MLD中潜在的、与临床相关的重要部分非常重要,但显然不太适合治疗。
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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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