Autoimmune encephalitis update

Abstract

Cancer-associated immune-mediated disorders of the central nervous system are a heterogeneous group. These disorders include the classic paraneoplastic neurologic disorders and the more recently described autoimmune encephalitis associated with antibodies to neuronal cell-surface or synaptic receptors that occur with and without a cancer association. Autoimmune encephalitis is increasingly recognized as the cause of a variety of neuropsychiatric syndromes that can be severe and prolonged. In contrast to the classic paraneoplastic disorders that are poorly responsive to tumor treatment and immunotherapy, autoimmune encephalitis often responds to these treatments, and patients can have full or marked recoveries. As early treatment speeds recovery, reduces disability, and decreases relapses that can occur in about 20% of cases, it is important that the immune pathogenesis of these disorders is recognized.

Keywords: antibodies; autoimmune; encephalitis; paraneoplastic; synaptic antigens.

Fig. 1.

Comparative immunolabeling of antibodies to cell-surface and intracellular antigens. Panels A and B show the dentate gyrus of hippocampus immunostained with CSF from a patient with NMDA receptor antibodies (A), and the CSF of a patient with Ri antibodies (B). Note that the NMDA receptor antibodies bind the neuropil (areas that contain neuronal processes and synapses), while the Ri antibodies bind to the nuclei of neurons. Scale bar in (B) = 50 μm. Panels C and D show cultures of dissociated rat hippocampal neurons incubated with the CSF of the patient with NMDA receptor antibodies (C) and the CSF of the patient with Ri antibodies (D). The NMDA receptor antibodies bind to cell-surface (extracellular) epitopes of the NMDA receptor, while the Ri antibodies show no binding because they do not penetrate live neurons. Scale bar in (D) = 20 μm.