Immune-mediated disorders

Abstract

Paraneoplastic and autoimmune encephalitis comprise a group of immune-mediated disorders that are associated with different immune effector mechanisms. Classic paraneoplastic neurologic syndromes are triggered by an antitumor immune response. The disease is considered to result from a T-cell response; in addition, patients harbour high titers of autoantibodies against intracellular antigens that are considered as epiphenomenon but are useful diagnostic markers. Neuropathology consists of T-cell-dominated inflammation, marked neuronal loss, and microglial activation with upregulation of HLA-DR. In the last decade, an increasing number of diseases associated with autoantibodies against neuronal surface antigens have been described. There is strong evidence that these autoantibodies are pathogenic and the associated syndromes are generally termed as antineuronal autoimmune encephalitis. Patients typically present with limbic, multifocal, or diffuse encephalitis and respond to immunotherapy. Neuropathologic descriptions are restricted to few biopsy and autopsy specimens and show mild inflammatory infiltrates and microglial activation, together with reduced expression of the respective target antigens, immunoglobulin deposits, and a variable degree of complement activation. Other putative autoimmune disorders of the central nervous system include, among others, Rasmussen encephalitis, chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS), acute cerebellitis, Susac syndrome, and Hashimoto encephalitis. While pathologic studies suggest an immune-mediated disease for Rasmussen encephalitis, CLIPPERS, acute cerebellitis, and Susac syndrome, neuropathologic descriptions of Hashimoto encephalitis are rare and the pathogenesis deserves further study.

Keywords: CLIPPERS; NMDAR antibody; Rasmussen encephalitis; Susac syndrome; autoimmune encephalitis; neuropathology; paraneoplastic neurologic syndrome.