法布里病患者脑白质病变的发展及临床后果：系统综述。

Development and clinical consequences of white matter lesions in Fabry disease: a systematic review.

机构信息

Amsterdam UMC, University of Amsterdam, Department of Endocrinology and Metabolism, Meibergdreef 9, Amsterdam, the Netherlands.

出版信息

Mol Genet Metab. 2018 Nov;125(3):205-216. doi: 10.1016/j.ymgme.2018.08.014. Epub 2018 Sep 5.

DOI:10.1016/j.ymgme.2018.08.014

PMID:30213639

Abstract

BACKGROUND

Fabry disease (FD) is a rare lysosomal storage disorder that might result in, amongst other complications, early stroke and white matter lesions (WMLs). More insight in WMLs in FD could clarify the role of WMLs in the disease presentation and prognosis in FD. In this systematic review we assessed the prevalence, severity, location and course of WMLs in FD. We also systematically reviewed the evidence on the relation between WMLs, disease characteristics and clinical parameters.

METHODS

We searched Pubmed, EMBASE and CINAHL (inception to Feb 2018) and identified articles reporting on FD and WMLs assessed with MRI. Prevalence and severity were assessed for all patients combined and divided by sex.

RESULTS

Out of 904 studies a total of 46 studies were included in the analyses. WMLs were present in 46% of patients with FD (581 out of 1276 patients, corrected mean age: 38.8 years, range 11.8-79.3) and increased with age. A total of 16.4% of patients (31 out of 189 patients, corrected mean age: 41.1 years, range 35.8-43.3 years) showed substantial confluent WMLs. Men and women showed comparable prevalence and severity of WMLs. However, men were significantly younger at time of WML assessment. Patients with classical FD had a higher chance on WMLs compared to non-classical patients. Progression of WMLs was seen in 24.6% of patients (49 out of 199 patients) during 38.1 months follow-up. Progression was seen in both men and women, with and without enzyme replacement therapy, but at an earlier age in men. Stroke seemed to be related to WMLs, but cerebrovascular risk factors, cardiac and renal (dys)function did not. Pathology in the brain in FD seemed to extend beyond the WMLs into the normal appearing white matter.

CONCLUSIONS

A significant group of FD patients has substantial WMLs and male patients develop WMLs earlier compared to female patients. WMLs could be used in clinical trials to evaluate possible treatment effects on the brain. Future studies should focus on longitudinal follow-up using modern imaging techniques, focusing on the clinical consequences of WMLs. In addition, ischemic and non-ischemic pathways resulting in WML development should be studied.

摘要

背景

法布里病（Fabry disease，FD）是一种罕见的溶酶体贮积病，可导致早期中风和白质病变（white matter lesions，WML）等并发症。进一步了解 FD 中的 WML 可以阐明 WML 在 FD 发病机制和预后中的作用。在这项系统评价中，我们评估了 FD 中 WML 的患病率、严重程度、位置和病程。我们还系统地回顾了 WML 与疾病特征和临床参数之间关系的证据。

方法

我们检索了 Pubmed、EMBASE 和 CINAHL（从创建到 2018 年 2 月），并确定了报告 MRI 评估 FD 和 WML 的文章。综合所有患者以及按性别进行了患病率和严重程度的评估。

结果

在 904 项研究中，共有 46 项研究纳入分析。FD 患者的 WML 患病率为 46%（1276 例患者中有 581 例，校正平均年龄：38.8 岁，范围 11.8-79.3 岁），且随年龄增长而增加。共有 16.4%的患者（189 例患者中有 31 例，校正平均年龄：41.1 岁，范围 35.8-43.3 岁）存在大量融合性 WML。男性和女性的 WML 患病率和严重程度相当。然而，男性在 WML 评估时的年龄明显较小。与非经典患者相比，经典 FD 患者发生 WML 的几率更高。在 38.1 个月的随访中，有 24.6%的患者（199 例患者中有 49 例）的 WML 出现进展。进展在男性和女性、有和没有酶替代治疗的患者中均可见，但在男性中更早出现。中风似乎与 WML 有关，但脑血管危险因素、心脏和肾脏（功能）障碍与 WML 无关。FD 中的脑病理学似乎超出了 WML 进入正常外观的白质。