An Overview of Autoimmune and Paraneoplastic Encephalitides

Abstract

The understanding of the manifestations, mechanisms, and management of autoimmune encephalitis has expanded dramatically in recent decades. Immune-mediated encephalitides are comparable in incidence and prevalence to infectious etiologies, and are associated with significant morbidity, especially when there is a delay in recognition and treatment. As such, clinicians from many specialties must develop a functional understanding of these disorders. Herein we provide an overview of the autoimmune and paraneoplastic encephalitides, including those associated with either intracellular or cell surface/synaptic neuronal autoantibodies. After briefly reviewing the current understanding of the pathobiology of autoimmune encephalitis, we combine a neuroanatomical approach with specific antibody syndromes to provide the reader with a clinically relevant review of these disorders. The clinical manifestations, diagnosis, and management of autoimmune encephalitis are reviewed, with an emphasis on clinical relevance. We also introduce updates in the field, including autoimmune encephalitis associated with novel cancer immunotherapies, infectious triggers of autoimmune encephalitis, and autoimmune encephalitis with demyelinating overlap syndromes.

A young man in “double-trouble”: Hallucinations and cranial nerve palsies

“…The differential diagnosis for encephalitis (table 2) includes primarily infectious (common causes include herpes simplex virus-1, varicella zoster zirus, and enterovirus) and immune-mediated etiologies (NMDA receptor [NMDAR] encephalitis, leucine-rich glioma inactivated-1 encephalitis, among others). 2,3…”

Modeling of the immune response in the pathogenesis of solid tumors and its prognostic significance

“…During the development of cancer, immunological homeostasis is disturbed. On the one hand, some tumors increase immunopathological activity, predisposing them to the occurrence of paraneoplastic syndromes by the release of highly immunogenic factors, which leads to dysfunction of specific organs [3]. On the other hand, tumor promotion is usually accompanied by an increased frequency of infection due to the occurrence of secondary immune deficits, which is also associated with a more severe course of infection and an increased mortality among treated patients [4][5][6][7].…”

Emergency Evaluation and Management of Encephalitis and Myelitis in Adults

“…14 AIE typically presents in an acute to subacute time frame. 15 Some features that suggest AIE include new psychiatric manifestations, movement disorders, or faciobrachial dystonic seizures. 15 However, historical clues can be misleading.…”

“…15 Some features that suggest AIE include new psychiatric manifestations, movement disorders, or faciobrachial dystonic seizures. 15 However, historical clues can be misleading. For example, symptoms of upper respiratory tract infection commonly precede both NMDAR encephalitis 16 and HSV-1 encephalitis (HSVE).…”

“…12 When there are features that might suggest AIE 42 and/or infection has been excluded, comprehensive antibody testing should be performed from both serum and CSF. 15 Given the clinical overlap of AIE syndromes (especially early in the illness), comprehensive rather than focused testing is suggested, although syndrome-based panels are now available.…”