ABSTRACT
Paraneoplastic neurological syndromes (PNS) represent the remote effects of cancer not due to the primary or secondary malignancy. They are immune-mediated and associated with a range of antibodies; onconeuronal or anti-neuronal. Lung, breast, ovarian, and testicular cancers are the commonest malignancies associated with PNS. The presence of these antibodies mandates a rigorous search for the relevant associated malignancy, which may be occult. The commonest PNS are cerebellar degeneration, limbic encephalitis, and encephalomyelitis.
The new biologic and immunotherapy treatments are associated with a wide range of CNS neurotoxicities. Posterior reversible encephalopathy syndrome (PRES) is seen in patients with leukaemia and lymphoma and is associated with the use of certain anti–vascular endothelial growth factor (VEGF) agents. Progressive multifocal leukoencephalopathy (PML) is a progressive white matter disorder associated with use of monoclonal antibody therapy against CD20 and is associated with leukaemia and lymphoma. Hypophysitis is a well-recognized complication of immune checkpoint inhibitors, such as ipilimumab.
White matter toxicity is associated with the use of methotrexate and several other agents, including 5-fluorouracil and capecitabine.
Radiation to the CNS is associated with white matter changes, which associate with cognitive decline. Radiation-induced haemorrhagic lesions of intracerebral cavernous malformations and cerebral microbleeds are long-term sequelae. There is an increased risk of secondary intracranial tumours, gliomas, and meningiomas after cranial irradiation in childhood.
