Cerebral Atrophy and Leukoencephalopathy Following Cranial Irradiation

The delayed adverse neurologic sequelae of radiation therapy, including radiation leukoencephalopathy, hydrocephalus, and cerebral atrophy, represent an increasingly important problem as advances in cancer therapy lead to prolonged patient survival. A variety of pathophysiologic mechanisms for late radiation injury have been proposed, including neurovascular injury, impaired neurogenesis secondary to neural progenitor cell injury, and inflammatory changes. Patient age and comorbidities, as well as radiation dose schedule and the use of concurrent chemotherapy, all appear to be important determinants of long-term outcome. Leukoencephalopathy, or diffuse white matter injury, is associated with progressive and irreversible neurocognitive decline, as well as personality changes, neuropsychiatric abnormalities, Parkinsonism, tremor, and seizures. Hydrocephalus is a common sequela, leading to cognitive impairment, gait instability and urinary incontinence. Radiation therapy is also known to result in progressive brain volume loss, with particular vulnerability in regions associated with higher-order cognitive performance and endogenous neural repair mechanisms. Management strategies are supportive, including CSF diversion in cases of hydrocephalus and neurostimulants and acetylcholinesterase inhibitors in radiation-associated dementia. More work on strategies aimed at neuroprotection and brain repair is needed to serve this growing patient population.