Changes in the Central Nervous System Following Irradiation with 23-mev X-Rays from the Betatron

During the past three years, studies have been in progress to determine and analyze the effects of x-rays on the normal brain of the monkey and on tumors of the central nervous system of man. Although these studies have been carried out primarily with 23-mev x-rays, produced by the University of Illinois betatron, additional comparative studies utilizing 200 and 400 kv. x-rays have also been undertaken. Our findings, to date, would indicate that the brain of both monkey and man is more radioresponsive than previously supposed, and that the pathological changes produced by these radiations are due to a direct effect upon the neural elements. These observations are definitely contradictory to the observations made by previous investigators (1–5) who have irradiated the central nervous system of a variety of animal species, including man (6). In general, these authors have concluded (a) that the central nervous system is highly radioresistant, in that it requires many thousands of roentgens to produce any recognizable pathological effects, and (b) that any changes produced by the radiations are secondary to an interruption of the vascular bed rather than to a direct injurious effect upon the neural elements. An exception to the second concept was made by Davidoff and co-workers (7), who exposed the brains and spinal cords of the adult monkey (Macacus rhesus), through an open wound, to single doses of 200 kv. x-rays, from 1,000 to 5,000 r (as measured in air), and demonstrated that the nervous and glial cells were affected, whereas the changes in the blood vessels were surprisingly slight in degree. With reference to the human brain, O'Connell and Brunschwig (8) and Wachowski and Chenault (9) noted, in their patients receiving x-ray therapy, that the radiation produced changes in both the neural elements and some of the vessels but that the neural changes were primary effects rather than a result of the vascular changes noted. In addition to our observation that the central nervous system is more radioresponsive and that the neural elements respond directly to the radiation, we have noted a very striking selective destruction of the white matter occurring months to a year or more after irradiation. This readily demonstrable radioselectivity for the white matter begins as a demyelinating process and proceeds, with time and increasing dose, to an actual necrosis of the myelin and axons, whereas, in comparison, the irradiated neurons show only moderate changes. This phenomenon of delayed radionecrosis of the white matter is not related to the occlusion of vascular channels, but is due to an actual destruction of the myelin and axons. It has appeared in our experimental animals, as well as in our patients with neoplasms who have received x-ray therapy with either the betatron or with standard x-ray machines of lower energies.