Autoimmune Global Amnesia as Manifestation of AMPAR Encephalitis and Neuropathologic Findings.

Abstract

OBJECTIVE:

To report an unusual clinical phenotype of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) encephalitis and describe associated neuropathologic findings.

METHODS:

We retrospectively investigated 3 AMPAR encephalitis patients with autoimmune global hippocampal amnesia using comprehensive cognitive and neuropsychologic assessment, antibody testing by in-house tissue-based and cell-based assays, and neuropathologic analysis of brain autopsy tissue including histology and immunohistochemistry.

RESULTS:

Three patients presented with acute-to-subacute global amnesia without affection of cognitive performance, attention, concentration, or verbal function. None of the patients had epileptic seizures, change of behavior, personality changes, or psychiatric symptoms. The MRI was normal in 1 patient and showed increased fluid-attenuated inversion recovery/T2 signal in the hippocampus in the other 2 patients. Two patients showed complete remission after immunotherapy. The one patient who did not improve had an underlying adenocarcinoma of the lung and died 3.5 months after disease onset because of tumor progression. Neuropathologic analysis of the brain autopsy revealed unilateral hippocampal sclerosis accompanied by mild inflammatory infiltrates, predominantly composed of T lymphocytes, and decrease of AMPAR immunoreactivity.

CONCLUSION:

AMPAR antibodies usually associate with limbic encephalitis but may also present with immune responsive, acute-to-subacute, isolated hippocampal dysfunction without overt inflammatory CSF or MRI changes.

• Authors: Gerda Ricken, Tobias Zrzavy, Stefan Macher, Patrick Altmann, Johannes Troger, Kim Kristin Falk, Andreas Kiefer, Andreas Fichtenbaum, Goran Mitulovic, Helmut Kubista, Klaus-Peter Wandinger, Paulus Rommer, Thorsten Bartsch, Thomas Berger, Jörg Weber, Frank Leypoldt, Romana Höftberger
• Journal: Neurology(R) neuroimmunology & neuroinflammation (Neurol Neuroimmunol Neuroinflamm) Vol. 8 Issue 4 (07 2021) ISSN: 2332-7812 [Electronic] United States
• PMID: 34016735 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Chemical References

• Autoantibodies
• Receptors, AMPA

Topics

• Adult
• Aged
• Amnesia (etiology, immunology, pathology, physiopathology)
• Autoantibodies (blood, cerebrospinal fluid)
• Autoimmune Diseases of the Nervous System (complications, immunology, pathology, physiopathology)
• Encephalitis (complications, immunology, pathology, physiopathology)
• Female
• Hippocampus (immunology, pathology, physiopathology)
• Humans
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Receptors, AMPA (immunology)
• Retrospective Studies