Neurological Complications of Anderson-Fabry Disease
Neurological Complications of Anderson-Fabry Disease
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DOI：
10.2174/13816128113199990387
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发表时间：
2013-10-01
影响因子：
3.1
通讯作者：
Pinto, Antonio
中科院分区：
文献类型：
--
作者：
Tuttolomondo, Antonino;Pecoraro, Rosaria;Pinto, Antonio
AFD 的特征性临床表现，如肢端感觉异常、血管角化瘤、角膜混浊、少汗症和无汗症、胃肠道症状、肾功能障碍和心脏功能障碍，可能发生在男性和女性患者中，尽管患有 AFD 的杂合子女性通常受影响程度较轻。最突出的中枢神经系统表现包括脑血管事件，例如短暂性脑缺血发作（TIA）和（复发性）中风。大多数情况下，AFD 的中枢神经系统并发症归因于脑血管病变，包括解剖异常。Fabry 患者的自然史包括短暂性脑缺血和中风，即使是非常年轻的男女也是如此。该机制部分归因于血管内皮细胞中 Gb-3 的积累。 MRI 上出现白质病变 (WML)。男性和女性都可以安全地接受酶替代治疗；因此，应考虑对年轻卒中人群进行法布里病筛查。然而，没有关于治疗对死亡率和发病率影响的硬数据。 Anderson-Fabry 病中风对 721 名年龄在 18-55 岁的隐源性中风患者进行的研究表明，该组中法布里病的患病率很高：男性为 5% (21/432)，女性为 3% (7/289)。结合两性的结果显示，先前不明原因的中风年轻患者中有 4% 患有法布里病，相当于一般年轻中风患者人群的约 1-2%。法布里病中描述了脑微血管病变和大血管病变。 FD 的尸检研究报告了神经元三酰基神经酰胺在选择性皮质和脑干区域（包括海马）的积累，但迄今为止尚未研究临床替代物以及这些发现的临床相关性。法布里病 (FD) 的另一个神经学特征包括小纤维神经病以及伴有过早中风的脑微血管病和大血管病。头颅 MRI 显示幼年时出现进行性白质病变 (WML)、脑枕信号强度增加以及较大血管的扭曲和扩张。传统 MRI 显示 FD 过程中由于脑血管病变导致白质病变 (WML) 逐渐加重。另一项研究旨在量化临床上受影响的男性和女性 FD 患者的大脑结构变化。法布里病的周围神经病变表现为神经性疼痛、冷热感觉减弱以及可能的胃肠道紊乱。法布里病患者在生命的第一个十年末或青春期开始出现疼痛。年仅 6 岁的儿童抱怨疼痛，通常与热病和运动耐量降低有关。患者将疼痛描述为烧灼感，通常伴有深度疼痛或感觉异常。有些患者还伴有关节疼痛。很大一部分法布里病患者出现神经精神症状的风险增加，例如抑郁和神经心理缺陷。由于躯体和心理损伤，法布里病患者的健康相关生活质量 (QoL) 显着降低。对年轻中风患者进行法布里病的针对性筛查似乎可以发现未被识别的病例，因此很可能在未来被推荐为常规检查。此外，缺血性中风与炎症和动脉僵硬度有关，并且没有研究探讨房颤疾病和脑血管疾病患者的这种关系，因此该主题可能代表未来可能的研究方向。
Characteristic clinical manifestations of AFD such as acroparesthesias, angiokeratoma, corneal opacity, hypo/ and anhidrosis, gastrointestinal symptoms, renal and cardiac dysfunctions can occur in male and female patients, although heterozygous females with AFD usually seem to be less severely affected. The most prominent CNS manifestations consist of cerebrovascular events such as transient ischaemic attacks (TIAs) and (recurrent) strokes. For the most part, CNS complications in AFD have been attributed to cerebral vasculopathy, including anatomical abnormalities.The natural history of Fabry patients includes transitory cerebral ischaemia and strokes, even in very young persons of both genders. The mechanism is partly due to vascular endothelial accumulation of Gb-3. White matter lesions (WML) on occur MRI. Both males and females can be safely treated with enzyme replacement; and thus screening for Fabry disease of young stroke populations should be considered. There are, however, no hard data of treatment effect on mortality and morbidity. Stroke in Anderson-Fabry disease study of 721 patients with cryptogenic stroke, aged 18-55 years, showed a high prevalence of Fabry disease in this group: 5% (21/432) of men and 3% (7/289) of women. Combining results of both sexes showed that 4% of young patients with stroke of previously unknown cause had Fabry disease, corresponding to about 1-2% of the general population of young stroke patients. Cerebral micro-and macro-vasculopathy have been described in Fabry disease. Neuronal globotriaosylceramide accumulation in selective cortical and brain stem areas including the hippocampus has been reported by autopsy studies in FD, but clinical surrogates as well as the clinical relevance of these findings have not been investigated so far. Another Neurologic hallmark of Fabry disease (FD) includes small fiber neuropathy as well as cerebral micro-and macroangiopathy with premature stroke. Cranial MRI shows progressive white matter lesions (WML) at an early age, increased signal intensity in the pulvinar, and tortuosity and dilatation of the larger vessels. Conventional MRI shows a progressive load of white matter lesions (WMLs) due to cerebral vasculopathy in the course of FD. Another study has been conducted to quantify brain structural changes in clinically affected male and female patients with FD. The peripheral neuropathy in Fabry disease manifests as neuropathic pain, reduced cold and warm sensation and possibly gastrointestinal disturbances. Patients with Fabry disease begin having pain towards the end of the first decade of life or during puberty. Children as young as 6 years of age have complained of pain often associated with febrile illnesses with reduced heat and exercise tolerance. The patients describe the pain as burning that is often associated with deep ache or paresthesiae. Some patients also have joint pain. A high proportion of patients with Fabry disease is at increased risk of developing neuropsychiatric symptoms, such as depression and neuropsychological deficits. Due to both somatic and psychological impairment, health-related quality of life (QoL) is considerably reduced in patients with Fabry disease.Targeted screening for Fabry disease among young individuals with stroke seems to disclose unrecognized cases and may therefore very well be recommended as routine in the future. Furthermore, ischemic stroke is related to inflammation and arterial stiffness and no study had addressed this relationship in patients with AF disease and cerebrovascular disease, so this topic could represent a possible future research line.