Scollard David M
National Hansen's Disease Programs, LSU-SVM, Skip Bertman Dr. Baton Rouge, LA 70803, USA.
Lepr Rev. 2008 Sep;79(3):242-53.
The steps in the pathogenesis of nerve injury in leprosy are depicted in Figure 1. Localisation of M. leprae to nerve, Schwann cell infection & responses, as yet unknown mechanisms of injury, axonal atrophy, and finally demyelination. These steps, and the mechanisms responsible for them, occur quickly in the course of this disease (as noted, even the earliest diagnostic lesions have sensory abnormalities), but they are also chronic processes that may contribute to progressive nerve injury over a period of many years unless interrupted by treatment, and even after cure of the infection in some patients. A common feature throughout this pathogenesis is inflammation--within and around the nerve. Inflammation is not only defined by its chemical mediators such as cytokines and chemokines, but by one of the most basic phenomena of inflammation--edema. The extent to which edema might contribute to nerve injury in leprosy has not been reviewed because it has not been studied in nerves affected by leprosy, although clinically, surgeons who perform neurolysis are convinced that they are decompressing nerves sustaining injury due to increased (edematous?) pressure. Inflammation in and around nerves is undoubtedly driven, in part, by the immunological responses in each of the portions of the immunologic spectrum of leprosy, but some inflammatory phenomena may be non-specific inflammation related to infection and foreign material (i.e., mycobacterial components). Few if any fixed associations can be made between the steps outlined in this conceptual framework of events; even the depicted sequence of these events is uncertain. Considerable additional data is needed to determine the connections between these processes and their underlying mechanisms. Additionally, although much emphasis is given to myelinated fibres (and demyelination) in studies of the biology of leprosy neuropathy, the small, sensory fibres in the skin are not myelinated. Additional studies of mechanisms of injury to these nerves is required. The results of all of these studies can be reasonably expected to identify new points for clinical intervention in--and possibly the prevention of--nerve injury in leprosy.
麻风病神经损伤的发病机制步骤如图1所示。麻风杆菌定位于神经，施万细胞感染及反应，尚不清楚的损伤机制，轴突萎缩，最终脱髓鞘。这些步骤及其相关机制在该疾病过程中迅速发生（如前所述，即使是最早的诊断性病变也有感觉异常），但它们也是慢性过程，可能导致多年来的进行性神经损伤，除非通过治疗中断，甚至在一些患者感染治愈后也是如此。在整个发病机制中一个共同特征是神经内和神经周围的炎症。炎症不仅由其化学介质如细胞因子和趋化因子来定义，还由炎症最基本的现象之一——水肿来定义。尽管临床上进行神经松解术的外科医生确信他们正在为因压力增加（水肿性？）而受损的神经减压，但水肿在多大程度上可能导致麻风病神经损伤尚未得到综述，因为尚未在受麻风病影响的神经中进行研究。神经内和神经周围的炎症无疑部分是由麻风病免疫谱各部分的免疫反应驱动的，但一些炎症现象可能是与感染和异物（即分枝杆菌成分）相关的非特异性炎症。在这个概念性事件框架中概述的步骤之间几乎无法建立固定的关联；甚至这些事件的描述顺序也不确定。需要大量额外的数据来确定这些过程及其潜在机制之间的联系。此外，尽管在麻风病神经病变生物学研究中非常强调有髓纤维（和脱髓鞘），但皮肤中的小感觉纤维是无髓的。需要对这些神经的损伤机制进行更多研究。可以合理预期所有这些研究的结果将为麻风病神经损伤的临床干预——甚至可能是预防——找到新的切入点。
