Autoimmune Encephalopathies and Dementias

This article describes the methods of diagnosis and management of autoimmune encephalopathies and dementias. The expedited distinction of autoimmune encephalopathies and dementias from neurodegenerative disorders is important because treatment is most effective at the early stage of illness.

The spectrum of antibody biomarkers of treatable autoimmune encephalopathies continues to broaden and now includes antibodies targeting glutamate receptors (N-methyl-D-aspartate [NMDA] and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid [AMPA]), γ-aminobutyric acid A and B (GABA-A and GABA-B) receptors, glycine receptors, potassium channel complexes (Kv1, which includes leucine-rich, glioma inactivated 1 [LgI1], contactin-associated proteinlike 2 [CASPR2], and unknown specificity, and Kv4.2, which includes dipeptidyl-peptidase 6 [DPPX]), and glutamic acid decarboxylase 65 (GAD65). Early treatment of certain autoimmune encephalopathies with rituximab or cyclophosphamide improves outcome when corticosteroids, IV immunoglobulin (IVIg), and plasma exchange have proven ineffective.

Despite the progress made in diagnostics, in many instances, patients with immunotherapy-responsive encephalopathies and dementias are seronegative for encephalitis-specific antibodies. Other clues to an autoimmune cause include a subacute symptom onset, rapid progression, personal history of autoimmunity or cancer, an inflammatory CSF, non-neural antibodies detected in serum, and a response to immunotherapy.