Schiffmann Raphael, Moore David F
Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, Building 10, Room 3D03, National Institutes of Health, Bethesda, Maryland, 20892-1260, USA
Section of Neurology, Department of Internal Medicine, University of Manitoba, Winnipeg, Canada
The neurological manifestations of Fabry disease include both peripheral nervous system and CNS involvement, with globotriaosylceramide accumulation found in Schwann cells and dorsal root ganglia together with deposits in CNS neurones. The main involvement of the CNS is attributable to cerebrovasculopathy, with an increased incidence of stroke. The abnormal neuronal accumulation of glycosphingolipid appears to have little clinical effect on the natural history of Fabry disease, with the possible exception of some reported mild cognitive abnormalities. The pathogenesis of Fabry vasculopathy remains poorly understood, but probably relates, in part, to abnormal functional control of the vessels, secondary to endothelial dysfunction as a consequence of α-galactosidase A deficiency. Obstructive vasculopathy, either primarily due to accumulation of glycolipid or secondary to consequent inflammation and confounding vascular risk factors, may develop in response to abnormal endothelial and vessel wall function, similar in some respects to that observed with accumulation of cholesterol-laden lipids during atherosclerosis. Involvement of the peripheral nervous system affects mainly small Aδ and C fibres, and is probably causally related to the altered autonomic function and neuropathic pain found in Fabry disease. Other related neurological problems include hypohidrosis and other abnormalities associated with nervous system dysfunction.
法布里病的神经学表现包括外周神经系统和中枢神经系统受累，在施万细胞和背根神经节中发现有球三糖基神经酰胺蓄积，同时中枢神经系统神经元中也有沉积物。中枢神经系统的主要受累归因于脑血管病变，中风发生率增加。糖鞘脂在神经元中的异常蓄积似乎对法布里病的自然病程几乎没有临床影响，可能除了一些报道的轻度认知异常外。法布里血管病变的发病机制仍知之甚少，但可能部分与血管功能的异常控制有关，这继发于α-半乳糖苷酶A缺乏导致的内皮功能障碍。阻塞性血管病变，要么主要由于糖脂蓄积，要么继发于随之而来的炎症和混杂的血管危险因素，可能是对内皮和血管壁功能异常的反应而发生，在某些方面类似于动脉粥样硬化期间富含胆固醇的脂质蓄积时观察到的情况。外周神经系统受累主要影响小的Aδ和C纤维，可能与法布里病中发现的自主神经功能改变和神经性疼痛有因果关系。其他相关的神经问题包括少汗症和与神经系统功能障碍相关的其他异常。
