Radiation injury to the CNS is manifest as three distinct clinical entities (15). During XRT, patients often experience fatigue and an increase in neurologic symptoms and signs, and death from brain herniation––especially after a large single dose, such as that delivered during stereotactic XRT––has been reported (16). The acute CNS radiation injury is generally considered to be secondary to edema and disruption of BBB (8, 17).
A self-limiting, delayed reaction known as Lhermitte’s syndrome is well recognized after XRT to the spinal cord. It occurs after a latent period of two to four months and is characterized by paresthesia in the back and extremities upon neck flexion. After cranial XRT, a corresponding syndrome characterized by somnolence has also been described (18). These syndromes typically last for a few months followed by complete clinical recovery. Transient demyelination is believed to be the underlying mechanism of these early delayed reactions.
Late effects, occurring after recovery from the early onset syndromes, are irreversible and most devastating, and thus are the most clinically important. Radiation injury to the spinal cord is associated with permanent motor and sensory deficits (15) and can be fatal if the damage occurs at the upper cervical level (19). In the brain, late effects include minor-to-severe neurocognitive deficits (20) and focal necrosis, the latter after higher doses (21). The systematic use of magnetic resonance imaging (MRI) leads to progressive and diffuse changes in white matter often after doses well below the threshold of necrosis (21, 22). The underlying histopathologic changes associated with these imaging findings and their relevance to the neurocognitive dysfunction observed after XRT are poorly understood.