Principles of autoimmune and paraneoplastic encephalitis

Abstract

The paraneoplastic and autoimmune encephalitides are now well-established entities. Detection of neural autoantibodies enables specific diagnoses, provides information on the underlying disease pathophysiology, immunological treatability and the likelihood of atumor being the underlying cause. This is true for the "high ranking" neural antibodies that have been established in the context of circumscribed clinical images and in consideration of large control groups, have been found in the same way by other laboratories and they respond to immunotherapy. The immune reaction can be triggered by tumors and virus encephalitides, e.g. N‑methyl-D-aspartate (NMDA) receptor antibodies. In some cases agenetic predisposition has been shown. Some antibodies are formed peripherally, others intrathecally. The route of the antibodies into the brain can be via the blood-brain barrier or cerebrospinal fluid (CSF). In the brain itself, the antibodies lead to an internalization of antigenic receptors, such as NMDA and α‑amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, or to nerve-destroying activation of the classical complement cascade. In other conditions, cytotoxic T cells are at the core of the pathophysiology. For diagnostic purposes, the testing of CSF-serum pairs with broad spectrum antigen panels is recommended. Therapeutically, the aim is to suppress the production of pathogenic antibodies or even to eliminate them directly. Asequence of first-line treatment (steroids, intravenous immunoglobulins and/or apheresis) and second-line treatment (rituximab and/or cyclophosphamide) has been established.