Pathology of acute and chronic ischaemic neuropathy in atherosclerotic peripheral vascular disease

The peripheral nerve pathology in ischaemic limbs with atherosclerotic peripheral vascular diseases (PVD) is difficult to ascertain because of the limited number of reports. In addition, it has been debated whether chronic ischaemia per se could cause morphological abnormalities in peripheral nerves. In this prospective study, we examined pathological findings in the sural, saphenous, deep peroneal, superficial peroneal and tibial nerves, taken from seven acutely and nine chronically ischaemic amputated legs in which ischaemia was due to non-diabetic severe PVD. For morphological comparison, nerves were also taken from amputated legs without ischaemic disease and those in which PVD was associated with diabetes. In acutely ischaemic nerves, pathological changes were dependent upon the duration of ischaemia. Axonal degeneration of both myelinated and unmyelinated nerve fibres (MFs and UMFs) with occluded vessels was prominent, if acute ischaemia was present for > 24 h. Focal lesions, a hallmark of acute ischaemic neuropathy, were seen in both acute and chronic PVD nerves. Chronic PVD nerves also revealed considerable variations in the density of MFs between the fascicles of individual nerves and between the nerves of individual subjects: demyelination and remyelination, endoneurial oedema particularly at the subperineurial region, swollen endothelial cells, various but infrequent axonal changes, and relative preservation of UMFs were also seen. All pathological changes found in acute and chronic PVD nerves, except for a high rate demyelinated and remyelinated nerve fibres, have been described in experimental models of acute ischaemic/reperfusion injury. Demyelination could be induced by chronic ischaemia. Thus, pathological alterations in chronic ischaemic neuropathy may be due to the combined effects of acute ischaemia/reperfusion and chronic hypoxia.