Radiation injury of the nervous system occurs as a complication of x-ray therapy wherein tissue dosage has been excessive. Signs of injury may appear within hours or days of high-dosage irradiation in laboratory animals; in man, with the doses used therapeutically, the onset is delayed. Characteristically, a progressive neurological deficit develops following a latent period of many months or years after the termination of radiotherapy.
This complication occurs when irradiation has been directed at neoplasms of the brain or at other tumors in the head and neck. The spinal cord is also subject to injury from excessive radiation, whether directed at a primary cord tumor or at tumors overlying the spine and para-spinal regions, e.g., tumors of the thyroid or mediastinum. Peripheral nerves are relatively radio resistant but are injured also by high doses.
Pathology.
The response of the central nervous system to ionizing radiation can be recognized in three phases: an acute phase of meningoencephalitis, a period of apparent normalcy, and a period of late nerve cell damage, demyelination, and vascular change. The lesions in the nervous system attributed to irradiation are extensive in both white and gray matter. There are hyaline thickenings in the walls of blood vessels that may partially or completely occlude the lumen. There is a variable degree of cellular necrosis and degeneration of myelin. Astrocytosis and thickening of the leptomeninges are common.
The long latent period between the time of irradiation and the onset of progressive signs is poorly understood; it has been attributed to progressive ischemia due to gradual narrowing of the vascular lumen. Latent radiation effects in skin are readily attributable to vascular and connective tissue damage; this lends weight to the primary importance of the vascular injury in the brain, although it is likely that neuronal degeneration is not due to progressive ischemia alone. It has been suggested that autoimmune mechanisms play a role in the tissue damage that develops after a latent period.
Dosages OF Radiation Injury.
The precise tissue dosage that will induce radiation injury is uncertain. The minimal dose in Lindgren’s series of 71 cases that produced pathologic evidence of brain necrosis was 4500 to 5000 roentgens, with delivery through mediumsized fields over a period of 30 days. The spinal cord is vulnerable to somewhat lower doses; radiation myelopathy has been reported following 4000 r in 28 days directed toward the mediastinum. Boden has defined the tolerance of the brain-stem and spinal cord from a review of his own material. With small treatment fields of 10 by 7 cm. or less, tissue doses up to 4500 r in 17 days or their biologic equivalent seem to be tolerated by the cord and brainstem. With large fields, a tissue dose of 3500 r is considered as the maximal tolerance dose to the brainstem and cord. There is considerable biologic variation in susceptibility of normal tissue to radiation damage, and precise definition of the effects of various dosages on normal tissue is difficult.
Clinical Manifestations.
When radiotherapy has been administered to tumors close to, but sparing, the brain and spinal cord, the development of a focal neurological deficit after a latent period raises the possibility of radiation injury. Following radiotherapy to brain or spinal cord tumors, clinical improvement that persists for one to five years with subsequent regression suggests the possibility of late radiation damage to normal nervous tissue. Symptoms most often appear about a year after irradiation. The onset is insidious, and the rate of subsequent progress is unpredictable. The process may become arrested or may progress to cause a major cerebral hemispheric deficit or complete functional spinal cord transaction. The clinical differentiation between radiation injury and recurrent tumor growth may be very difficult and uncertain pending pathological confirmation at autopsy, and both may be coexistent. A repeated roentgenographic contrast study may help in differentiation. There is no specific therapy for radiation injury of the nervous system.
