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

Abstract

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.

Relationship between Ischemia and Neuropathy

“…Distal sensory changes and sometimes distal weakness are found. After acute ischemia, electrophysiological [60]and pathological [62]examination shows axonal degeneration of nerves of the distal portion of the limb. Sensory amplitudes are usually more severely affected [60, 61, 63, 64].…”

“…Complaints are predominantly sensory, whereas motor abnormalities are less frequent [95]. Severity rather than duration of ischemia plays a key role in the development of the neuropathy [62, 97]. There is a correlation between the severity of peripheral arterial disease and the number of patients with neuropathy [98].…”

“…Quantitative morphological studies have mostly been performed on nerve specimens removed from limbs after amputation because of gangrene or intractable pain. Both signs of demyelinization and axonal degeneration are seen [62, 97, 101, 102, 103, 104, 105, 106]. There is no agreement on selective vulnerability of a certain fiber size [62, 104, 105].…”

Effects of a Tumor Necrosis Factor-Alpha Inhibitor (Etanercept) on the Sciatic Nerve in a Hypoxic Ischemia-Induced Neonatal Rat Model

“…Many researchers have also reported that hypoxia/ischemia injury plays an important role in the development of peripheral neuropathy [3,4]. Morphologically, ischemic nerves reveal various pathological abnormalities, including demyelination and remyelination, axonal degeneration and regeneration, focal, multifocal, or diffuse loss of nerve fibers, and endoneurial edema [5].…”

Atherosclerosis and Peripheral Neurological Problems

“…1,4,5) However, no studies have indicated that atherosclerosis affects peripheral nerves in other (nonischaemic) parts of the body. In this study, patients with coronary artery disease showed a greater predisposition to peripheral neurological problems than those without such disease (44% versus 7% respectively).…”