Acute encephalopathy, consisting of somnolence, headache, nausea, vomiting, and exacerbation of preexisting deficits, usually develops days after initiation of RT and generally responds to corticosteroids. No specific neuroimaging findings are associated with acute injury. Early-delayed complications include the somnolence syndrome, characterized by drowsiness, fatigue, anorexia, irritability, and transitory cognitive disturbances primarily affecting attention and short-term memory. Neuroimaging at this time may be unchanged or show increased edema and contrast enhancement within the tumor bed that mimics tumor progression, termed pseudoprogression (Fig. 105.1). The exact frequency with which this phenomenon occurs is difficult to estimate because of varying criteria defined in different reports. However, it occurs in at least 10% to 20% of patients with glioblastoma receiving concurrent RT and temozolomide; it manifests most commonly 1 to 3 months posttreatment (although may occur later) and usually improves within a few months. Late injury is associated with focal radionecrosis (causing seizures, focal neurologic symptoms, and signs of increased intracranial pressure) and leukoencephalopathy (leading to cognitive dysfunction and severe dementia). Diffuse white matter changes and atrophy are seen in the neuroimaging in nearly all cases. Magnetic resonance imaging (MRI) does not distinguish between radiation necrosis and tumor progression. Metabolic and
perfusion imaging studies may help discriminate the two entities, but surgery remains the gold standard to confirm the diagnosis.

Radiation-induced damage to the spinal cord is categorized into early-delayed (6 weeks to 6 months) and late-delayed (>6 months) myelopathy. Acute worsening should prompt investigation for intratumoral hemorrhage or tumor progression. Early-delayed RT myelopathy is characterized clinically by Lhermitte sign that typically resolves spontaneously, with no distinctive imaging finding. Patients with late-delayed radiation myelopathy often presents with Brown-Séquard syndrome, spastic paraplegia with impaired sensory and autonomic functions. The condition may begin abruptly or insidiously and is most often irreversible. MRI demonstrates increase T2 hyperintensity and enhancement in the affected spinal cord levels.

Any cranial nerves may be involved if included in the radiation field. The hypoglossal nerve is the most vulnerable followed by the vagus nerve and the recurrent laryngeal nerve, believed to be due to absorption of higher amount of energy from RT to the neck region. Optic neuropathy results in painless and progressive visual loss or visual field constriction. The oculomotor, trochlear, trigeminal, abducens, and facial nerves are less vulnerable and can be affected from focal RT for skull base tumors. Trigeminal neuropathy is quite rare and may result from radiosurgery for vestibular schwannoma and trigeminal neuralgia. Radiation-induced injury to vestibulocochlear nerve is rare, except in RT for acoustic neuroma. Hearing impairment, especially at high frequency, may be due to changes in the cochlea and/or retrocochlear auditory pathway. Permanent damage to cranial nerves is rare and usually occurs due to delayed effect.

RT-induced brachial and lumbosacral plexopathies may result from treatment of breast, lung, and pelvic cancers. The usual presentation includes paresthesia and hypesthesia, followed by weakness and amyotrophy. Pain is usually relatively mild and occurs late in the course, as opposed to severe pain in patients with malignant plexopathy. Myokymia seen on electromyography and hypointensity in T1- and T2-weighted sequences and absence of mass on MRI suggest RT plexopathy.

RT can indirectly cause endocrine dysfunction such as hypothalamic-pituitary impairment resulting in hypothyroidism, hypogonadism, hyperprolactinemia, and panhypopituitarism; vascular damage leading
to stroke, hemorrhage, vascular malformations, and rarely, SMART syndrome (stroke-like migraine attacks after radiation therapy); and secondary tumors such as meningioma, glioma, and sarcoma.