Autoimmune Global Amnesia as Manifestation of AMPAR Encephalitis and Neuropathologic Findings

Abstract

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

Anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor encephalitis developed after ovarian cancer cytoreduction surgery: a case report and literature review

“…Severe symptoms such as consciousness and autonomic dysfunction are thought to be related to higher titers of AE antibodies. However, from the previous cases, we observed some patients presenting mild symptoms but with high titers in serum and/or CSF and some patients being in fatal status but had relatively lower titers [ 17 , 20 – 22 ]. We supposed that the inconsistency was due to the concurrent onconeural antibodies, and the tumor itself might also have an impact on the severity of symptoms.…”

Epilepsy, Immunity and Neuropsychiatric Disorders

“…Moreover, anti-AMPAR-IgG coexist with onconeural antibodies, such as SOX-1 antibodies, glutamic acid decarboxylase (GAD) antibodies, anti-neuronal auto-Abs, such as anti-NMDAR-IgG, and Hashimoto’s encephalopathy [ 109 ]. Furthermore, in AMPAR-IgG AIE, amnestic syndromes, in the absence of epileptic seizures and cognitive features, have also been reported, both as idiopathic and paraneoplastic forms [ 112 ]. CSF examination could demonstrate elevated levels of proteins, isolated or combined with lymphocytic pleocytosis [ 109 ].…”

“…Other findings include activated microglia, astrogliosis, and inflammatory changes in meninges and brain parenchyma. Proteins suggestive of neurodegeneration were not revealed as well as complement activation [ 112 ]. Anti-AMPAR-IgG AIE could benefit from steroids, IVIGs, or plasma exchange treatments.…”

Neural Surface Antibodies and Neurodegeneration: Clinical Commonalities and Pathophysiological Relationships

“…AMPAR [ 35 , 36 ] and GABABR [ 31 ] antibodies act causing internalization and block of the receptor, respectively. However, neuropathological evidence of T cell activation and inflammation [ 32 , 168 ] together with the evidence of hippocampal sclerosis and evolution in brain atrophy suggest the presence of additional mechanisms promoting neurodegeneration.…”