234 J. R. M. INNES AND A. CARSTEN 



ogists and radiotherapeutists. As Itabashi ct al. (1957) pointed out, when a 

 neoplasm has been the target for irradiation, neurologic signs which might 

 appear later have usually been attributed either to metastasis or extension 

 of the primary lesion, especially when there has been some apparent im- 

 provement. Further, many human cases may not be followed up after 

 x-irradiation of the spine; in others, autopsies may not be possible when 

 death occurs years later, or it may not be possible to examine the spinal cord 

 at autopsy. Some papers on delayed irradiation myelopathy are based largely 

 on clinical data, and the lesions have not been comprehensively studied. 

 Dynes and Smedal's series included 10 therapy cases, and Friedman (1954) 

 estimated that the incidence of delayed neurologic damage was 10% in 

 100 patients with testicular carcinoma whose spinal cord had received 

 5,000 rads or more. In all cases, subsequent to irradiation, there is a latent 

 period ranging from many months to many years, during which there are 

 no neurologic signs or symptoms due to irradiation. The clinical onset can 

 be abrupt or insidious, with a variable neurologic syndrome leading to 

 paraplegia and inevitably to death, although some patients have lived for 

 years with paraplegia (Dynes and Smedal, 1960). 



Lesions in the spinal cord in such cases have been variously reported as 

 radionecrosis, postirradiation myelitis, or myelopathy; but whatever the 

 designation, the damage can be devastating and appears no different from 

 that described by us (cf. Itabashi et al., 1957, one of the few papers describ- 

 ing spinal cord damage in man). In the delayed postirradiation process, it is 

 not the most superficial layers of nervous tissue which are most radiosensitive, 

 but the white matter in both brain and spinal cord. Neuroglial response has 

 varied according to different reports, but it can be absent or negligible, and 

 in some late lesions neuroglia must have been destroyed at a rate equal to 

 the damage to white matter or rendered incapable of response. In both the 

 human brain and cord, observers have commented on the difficulty of 

 separating the damage done specifically by the irradiation on tissue already 

 traumatized by another cause, such as a tumor. 



The fundamental question, still not answered, is whether the damage is 

 a direct effect of the radiation or an indirect one caused by a primary 

 change in vascular walls which leads to interference of the normal blood 

 supply, possibly then emanating from chronic hypoxia or ischemia. If it 

 were a direct effect, then the question arises as to what happens to the 

 neural tissue in the latent period before the eventual neurologic signs and 

 symptoms. Years ago, Scholz (Scholz et al., 1959) and Zeman (1955) ob- 

 served in such late lesions the deposition in and around vessels of an 

 "amyloid or paramyloid material," the nature of which has never been 

 unequivocally established by histochemical methods. The thickening of 

 vessel walls and subsequent constriction of lumina were thought to cause 



