Autoimmune dementia and encephalopathy.
Autoimmune dementia and encephalopathies (ADE) are complex disorders that can cause immune-mediated cognitive deficits and have confusing nomenclature. Presentation varies from acute limbic encephalitis to subacute or chronic disorders of cognition mimicking neurodegenerative dementia. It may occur as a paraneoplastic phenomenon or an idiopathic autoimmune phenomenon. The presence of a personal/family history of autoimmunity, inflammatory spinal fluid, serologic evidence of autoimmunity (neural or nonorgan-specific), or mesial temporal magnetic resonance imaging abnormalities are clues to diagnosis. Bedside cognitive assessment and/or detailed neuropsychologic testing are useful. Neural-specific autoantibodies, mostly discovered in the past two decades, may bind antigens on the cell surface (e.g., N-methyl-d-aspartate receptor autoantibodies) and are likely to be pathogenic, with treatment aimed at antibody-depleting agents often with success, while antibodies binding intracellular antigens (e.g., antineuronal nuclear autoantibody type 1 (ANNA1 or anti-Hu)) are a marker of a T-cell-mediated process and treated with T-cell-depleting immunotherapies, with variable responses. Detection and treatment of cancer (when present) are essential. High-dose corticosteroids are the initial treatment in most patients and may serve as a diagnostic test when the diagnosis is uncertain. Repeat cognitive testing after immunotherapy helps document objective improvements. Maintenance immunotherapy is recommended in those at risk for relapse. Prognosis is variable, but paraneoplastic ADE with antibodies to intracellular antigens have a worse prognosis. The field is still developing and future studies should provide guidelines for diagnosis and treatments.
Department of Neurology, Mayo Clinic, Rochester, MN, USA.
Eoin P
EP
Flanagan
Department of Neurology, Mayo Clinic, Rochester, MN, USA.
Daniel A
DA
Drubach
Department of Neurology, Mayo Clinic, Rochester, MN, USA. Electronic address: bboeve@mayo.edu.
Bradley F
BF
Boeve
D000912:Antibodies, Neoplasm / Q000378:metabolism; D001323:Autoantibodies / Q000378:metabolism; D020274:Autoimmune Diseases of the Nervous System / Q000150:complications / Q000276:immunology / Q000628:therapy; D003704:Dementia / Q000150:complications / Q000276:immunology / Q000628:therapy; D051959:ELAV Proteins / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D024642:Potassium Channels, Voltage-Gated / Q000276:immunology / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000276:immunology*
D000912:Antibodies, Neoplasm; D001323:Autoantibodies; D051959:ELAV Proteins; D024642:Potassium Channels, Voltage-Gated; D016194:Receptors, N-Methyl-D-Aspartate
Hashimoto's encephalopathy; NMDA receptor encephalitis; nonvasculitic autoimmune inflammatory meningoencephalitis; paraneoplastic encephalitis; progressive encephalomyelitis rigidity and myoclonus; steroid-responsive encephalopathy associated with autoimmune thyroiditis; voltage-gated potassium channel complex