The pathogenesis of radiation myelopathy: Widening the circle

Abstract

The fact that the spinal cord can react to insult in a limited number of ways is again demonstrated in the article by Powers et al. (6). These authors show that the canine spinal cord reacts to radiation in much the same way as other experimental animals and humans, and that dogs apparently have latent periods that are comparable with other large animals, with the exception of the pig, of course. The new findings in this report are the reactions of the meninges and the dorsal root ganglia. Although many attempts have been made to categorize radiation lesions of the spinal cord, no classification scheme has met with wide spread acceptance. The reasoning behind the attempts at categorization is that better definition of the histopathology may assist in better understanding of the pathogenesis. The reasons that this effort has been largely unsuccessful are (a) not enough analysis as been directed at the changes during the latent period, (b) after the injury has advanced far enough to cause signs, the histological lesions are varied in both age and morphology, and (c) the pathogenesis of many different types of insult lead to similar lesions in the CNS. In pathology as in art, diferent interpretations can be given to the same image. The fundamentals of the pathology of radiation myelopathy are: the lesions are nearly always confined to the white matter; the primary lesions are confined to the irradiated portion of the cord with dying back and Wallerian degeneration occurring outside the field; a mononuclear inflammatory response is often observed, vascular changes may include hyaline thickening, telangiectasia, fibrinoid necrosis, vascular occlusion, focal hemorrhage, and hemorrhagic necrosis; parenchymal responses include demyelination and gliosis; and white matter necrosis may occur without apparently significant vascular injury. We would like to address each of these fundamentals in turn. Because of the overwhelming propensity for changes to occur in the white matter, it is unlikely that extramedullary arteries or arterioles are significantly involved in the pathogenesis. The grey matter is exquisitely sensitive to disruption of its oxygen supply and would show any such arterial changes to a greater degree than the white matter. Because lesions tend to be located in lateral motor tracts and edema is often found in active lesions, it can be argued effectively that the vascular related changes are more typical of a venous lesion than an arterial one. Some support for this argument can be found in the study by Reinhold et al. (8) who observed that myelopathy patients had significantly lower blood pressure than the cohort of nonmyelopathy patients. The fact that the lesions of radiation myelopathy are confined to the irradiated field argues against a role for an autoimmune response. Furthermore, the autoimmune theory has difficulties explaining, as do other theories of the pathogenesis of this injury, why the white matter necrosis involves axonal degeneration as well as demyelination. The mononuclear inflammatory response that is frequently observed in radiation lesions of the spinal cord seem to be a more common finding in human cases than in experimental animals. If this is true, then it may indicate that there is some difference in the pathogenesis between the human and animal models of human radiation myelopathy. Because it is difficult to differentiate between infiltrating blood monocytes and reactive resident microglia, it is not possible to determine what fraction of literature reports of mononuclear infiltrates represents a traditional inflammatory response and what fraction is a microglial response. The interpretation of inflammatory/ immune responses is further complicated by the fact that it is commonly impossible to differentiate lymphocytes from glial cells in sections of formalin-fixed paraffin embedded tissue (3). The vascular contribution to the radiation damage of the spinal cord is still unresolved. The unambiguous vas-