X-IRRADIATION AND DELAYED MYELOMALACIA 235 



hypoxia or dynamic alterations in the \ascular walls resultins: in increased 

 capillary permeability and seeping through of plasma. This was considered 

 sufficient to account for the lesions in areas of neural substance supplied by 

 the afi'ected vessels. These themes have been discussed repeatedly (see 

 Zeman, 1955, and the most recent paper by Scholz et al., 1959). 



It is doubtful if experimental work has helped greatly, whether we are 

 dealing with brain or spinal cord ( Malamud vt al., 1954; ( Pennybacker and 

 Russell, 1948: Warren. 1943; Davidoff et al, 1938; Clemente and Hoist, 

 1954; McLaurin rt «/., 1955; Scholz ct al., 1959). Nor are the reasons hard 

 to find. The acute necrosis produced by massi\e doses of x-rays does not help 

 to explain the pathogenesis of the late delayed damage. After x-irradiation, 

 experimentalists ha\e noted the utterly unpredictable variations (a) of the 

 reaction in difl'erent animals of the same species and age, some animals 

 remaining unscathed under the same experimental conditions and dosimetry 

 which causes marked late lesions in others, lb) in the latent period before 

 nemologic signs de\elop. and c ) in the occurrence of the \ascular changes, 

 because thickening or deposition of "amyloid material" has not always 

 been observed to be associated with the neural lesion. 



An experimental approach with any animal species brings out that it 

 is different than working with established transmissible neurotropic infec- 

 tions which can be reasonably controlled — the dose of causal agent related 

 to a regular incubation period and a specific pathologic effect. The \ arying 

 latent periods (Table I) set a formidable barrier in designing an experiment 

 on a quantitative basis. Many animals may not develop neurologic signs or 

 lesions under the same conditions of experiment, and to determine this with 

 certainty, it might be necessary to wait much longer than 1 year. Little 

 progress toward the solution of the problem may be expected until a lesion 

 can be produced consistently in small animals, under controlled conditions 

 related to dosimetry and exact localization of exposure. Monkeys and dogs 

 can hardly be used in large numbers because of the expense invoked, 

 although delayed cerebral and spinal cord lesions have been produced in 

 both species, and more meticulous clinical obser\ations are f)ossible with the 

 larger animals. If this were possible, it might open the way for study of the 

 pathogenesis of the myelopathv by examination of a large series of animals 

 from a few days postirradiation up to a year or more. Of ecjual importance 

 would be more accurate determination of the minimal pathologic dose to 

 effect the spinal cord damage. Our obser\ations were made with these facts 

 in mind, and their importance may lie in the consistency of production of 

 spinal lesions in rats, together with the continuing study of the pathogenesis. 



The work was initiated by obser\ations on rats exposed to upper body 

 irradiation in which some clinical signs suggested the animals might be 

 suffering from myelitic pain, evidenced by irritability, sensiti\ity to touch, 



