In this chapter we review the CNS syndromes mediated by autoimmune or inflammatory mechanisms in patients with cancer. Paraneoplastic neurological syndromes (PNS) are considered to be immune-mediated disorders against proteins expressed by the tumour and nervous system. The autoimmune hypothesis is supported by the presence in serum and CSF of antibodies against neural proteins that are also expressed in the tumour. Less frequently the tumour does not express neuronal proteins but predisposes to immune dysregulation and autoimmune mechanisms. Novel cancer therapies that enhance anti-tumour immune responses frequently cause inflammatory CNS disorders. Immune checkpoint inhibitors have been associated with a wide range of immune-related adverse effects, including an increased incidence of PNS. Another type of cancer therapy is based on the use of T cells genetically engineered to express chimeric antigen receptors (CARs) that recognize molecules present on the surface of tumour cells. CAR T cell therapy can cause severe, potentially lethal, encephalopathy syndromes mediated by massive release of cytokines instead of autoimmune mechanisms. Post-transplant autoimmune encephalitis are rare disorders that mostly occur after allogeneic haematopoietic stem cell transplantation. They are related to graft versus host disease and, sometimes, they associate with antibodies against neuronal surface antigens.

About 20 years ago the group of diseases currently known as ‘autoimmune encephalitis’ or ‘antibody-mediated encephalitis’ was unknown and the entire field of ‘autoimmune neurology’ non-existent. Since then, 18 autoimmune encephalitis and the corresponding syndromes have been described, including 16 in which the antigens are expressed on the cell surface of neurons and two on the surface of glial cells. The characterization of these autoimmune encephalitis was facilitated by the cumulative knowledge provided by research on autoimmune disorders of the neuromuscular junction (myasthenia gravis and Lambert–Eaton myasthenic syndrome) and the paraneoplastic neurological syndromes. Up to 12.6 per 100,000 persons are affected by encephalitis annually. Of these, it has been estimated that 20–30% are caused by autoimmune mechanisms. In children the most frequent types of autoimmune encephalitis are acute disseminated encephalomyelitis (ADEM), anti-MOG, and anti-NMDAR encephalitis. In young adults, particularly women, anti-NMDAR encephalitis, and in late adulthood, anti-LGI1 encephalitis, are the most prevalent autoimmune encephalitis. The most frequently used classifications combine information related to three features: mechanisms of disease (cytotoxic T cell or antibody-mediated mechanisms), type of antigen (intracellular vs cell surface), and presence or absence of a tumour. The detection of a neoplasm frequently serves to categorize the autoimmune encephalitis as paraneoplastic.

In this chapter we review the CNS syndromes mediated by autoimmune or inflammatory mechanisms in patients with cancer. Paraneoplastic neurological syndromes (PNS) are considered to be immune-mediated disorders against proteins expressed by the tumour and nervous system. The autoimmune hypothesis is supported by the presence in serum and CSF of antibodies against neural proteins that are also expressed in the tumour. Less frequently the tumour does not express neuronal proteins but predisposes to immune dysregulation and autoimmune mechanisms. Novel cancer therapies that enhance anti-tumour immune responses frequently cause inflammatory CNS disorders. Immune checkpoint inhibitors have been associated with a wide range of immune-related adverse effects, including an increased incidence of PNS. Another type of cancer therapy is based on the use of T cells genetically engineered to express chimeric antigen receptors (CARs) that recognize molecules present on the surface of tumour cells. CAR T cell therapy can cause severe, potentially lethal, encephalopathy syndromes mediated by massive release of cytokines instead of autoimmune mechanisms. Post-transplant autoimmune encephalitis are rare disorders that mostly occur after allogeneic haematopoietic stem cell transplantation. They are related to graft versus host disease and, sometimes, they associate with antibodies against neuronal surface antigens.