AMPA-Receptor Antibody by CBA, Spinal Fluid
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
AMPA receptors are highly conserved mammalian ionotropic glutamate receptors that mediate most fast excitatory neurotransmission in the brain. Antibodies targeting the extracellular domains of either or both GluR 1 or GluR2 (GluA1 or GluA2) subunits have been reported in 10 patients with thymoma, breast carcinoma, or lung carcinoma (small-cell or non-small cell)-associated limbic encephalitis. Patients with limbic encephalitis present with seizures, memory loss, and mood and personality changes. Coexisting neural autoantibodies were detected in 3 of the 10 seropositive patients: CRMP 5-IgG, 1; AGNA/SOX1 IgG, 1; GAD65 antibody, 1. Antibody-depleting therapies afforded rapid improvements, but relapses were frequent after discontinuing immunotherapy. Testing of cerebrospinal fluid is helpful when serum testing is negative.
Evaluating new onset encephalopathy encompassing 1 or more of the following: confusional states, psychosis, delirium, memory loss, hallucinations, seizures, dyssomnias
The following accompaniments should prompt suspicion for autoimmune encephalopathy:
-Autoimmune stigmata (personal or family history, or signs of diabetes mellitus, thyroid disorder, vitiligo, poliosis [premature graying], myasthenia gravis, rheumatoid arthritis, systemic lupus erythematosus)
-History of cancer
-Smoking history (20+ pack years) or other cancer risk factors
-Inflammatory cerebrospinal fluid or isolated protein elevation
-Neuroimaging signs suggesting inflammation
Evaluating limbic encephalitis
Directing a focused search for cancer
Investigating encephalopathy appearing in the course or wake of cancer therapy, and not explainable by metastasis or drug effect
AMPA-R-IgG is a valuable serological marker of autoimmune encephalopathy and of a patient's immune response to cancer. This autoantibody is usually accompanied by subacute neurological symptoms and signs, and is not found in healthy subjects.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
A negative result does not exclude autoimmune encephalopathy or cancer.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
Lai M, Hughes EG, Peng X, et al: AMPA receptor antibodies in limbic encephalitis alter synaptic receptor location. Ann Neurol 2009;65(4):424-434