Neurotoxic effects are a well-known, delayed consequence of treatment of PCNSL with WBRT plus chemoradiation or with WBRT alone. They are more common in patients older than 60 years and those with underlying vascular risk factors. Patients typically present with subcortical dementia, gait ataxia, and incontinence. Less severely affected patients have problems with attention, executive function, memory (particularly verbal), and psychomotor speed. The MRI may show periventricular white matter abnormalities, cortical atrophy, and ventricular enlargement, but these radiographic changes do not always correlate with clinical symptoms. Pathological studies have demonstrated demyelination, neuronal loss, gliosis, and rarefaction of the white matter. Large-vessel atherosclerosis has been observed as well, implicating vascular injury and resultant tissue ischemia as one possible mechanism for neurotoxic effects. Although the pathophysiology of treatment-related neurotoxic effects is multifactorial, toxic effects to neural progenitor cells are hypothesized to have a central role.