Autoimmune Encephalitis Panel, Serum (Sendout)

Test Information: Encephalitis is a debilitating neurologic condition caused by infectious and autoimmune conditions that result in inflammation of the brain parenchyma. The identification of autoantibodies may augment a diagnosis of autoimmune encephalitis, but is not required for the diagnosis or initiation of therapy. The most frequently identified antibodies target NMDA-R. We recommend ordering NMDA Receptor IgG Antibody with Reflex, Serum (Sendout) [RNMDA] as first-line testing for autoimmune encephalitis prior to ordering this full panel.

Monitoring titers over time for these antibodies is not recommended; however, this recommendation is based on limited currently available literature.

Test Algorithm: Refer to Mayo's algorithm (linked below) for additional detail on tests and potential reflex tests included in this panel. Reflex testing may be performed at additional charge.

• Mayo Autoimmune/Paraneoplastic Encephalopathy Evaluation Algorithm, Serum

Ordering Guidance: Refer to Autoimmune Encephalitis Testing Recommendations or consult the Laboratory Medicine Resident on-call.

• The Mayo Antibody Prevalence in Epilepsy and Encephalopathy (APE²) Scorecard may be used to determine the likelihood of neural antibody positivity in patients with encephalopathy and/or seizures.

Ordering Requirements: Orders from UW Medicine Neurology Clinics are pre-approved. For all other orders, Laboratory Medicine Resident (LMR) approval is required.

Immunofluorescence assay (IFA): Amphiphysin Ab, Anti-Glial Nuclear Ab Type 1, Anti-Neuronal Nuclear Ab Type 1, Anti-Neuronal Nuclear Ab Type 2, Anti-Neuronal Nuclear Ab Type 3, CRMP-5-IgG, GFAP, mGluR1 Ab, Neurochondrin, NIF, Purkinje Cell Cytoplasmic Ab Type 1, Purkinje Cell Cytoplasmic Ab Type 2, Purkinje Cell Cytoplasmic Ab Type Tr, Septin-7, TRIM46 Ab, PDE10A Ab.

Cell-binding assay (CBA): AMPA-R Ab, CASPR2-IgG, GABA-B-R Ab, LGI1-IgG, NMDA-R Ab, IgLON5 Ab, DPPX Ab.

Radioimmunoassay (RIA): GAD65 Ab Assay

Reference Values:

Note: Includes reference values for panel tests only.

Neuron-restricted patterns of IgG staining that do not fulfill criteria for ANNA-1, ANNA-2, CRMP-5-IgG, PCA-1, PCA-2, or PCA-Tr may be reported as "unclassified anti-neuronal IgG." Complex patterns that include nonneuronal elements may be reported as "uninterpretable."

CRMP-5 titers lower than 1:240 are detectable by recombinant CRMP-5 Western blot analysis. CRMP-5 Western blot analysis will be done on request on stored serum (held 4 weeks). This supplemental testing is recommended in cases of chorea, vision loss, cranial neuropathy, and myelopathy. Call the Neuroimmunology Laboratory at 800-533-1710 to request CRMP-5 Western blot.

Interpretation: Neuronal, glial, and muscle autoantibodies are valuable serological markers of autoimmune encephalopathy and of a patient's immune response to cancer. These autoantibodies are usually accompanied by subacute neurological symptoms and signs are not found in healthy subjects. It is not uncommon for more than 1 of the following autoantibody specificities to be detected in patients with an autoimmune encephalopathy:

• Plasma membrane autoantibodies: N-methyl-D-aspartate (NMDA) receptor; 2-amino-3-(5-methyl-3-oxo-1,2- oxazol-4-yl) propanoic acid (AMPA) receptor; gamma-amino butyric acid (GABA-B) receptor; neuronal ACh receptor. These are all potential effectors of neurological dysfunction.

• Neuronal nuclear autoantibodies, type 1 (ANNA-1), type 2 (ANNA-2), or type 3 (ANNA-3)

• Neuronal or muscle cytoplasmic antibodies: amphiphysin, Purkinje cell antibodies (PCA-1) and PCA-2, CRMP-5, GAD65, or striational

Cautions:

Negative results do not exclude autoimmune encephalopathy or cancer.

This test does not detect Ma1 or Ma2 antibodies (also known as MaTa), which are sometimes associated with brainstem and limbic encephalitis in the context of testicular germ cell neoplasms. Scrotal ultrasound is advised for men who present with unexplained subacute encephalitis. To order Ma2 Antibody, refer to separate test guide #577.

Intravenous immunoglobulin (IVIg) treatment prior to the serum collection may cause a false-positive result.

Outside Laboratories: Centrifuge samples and transfer serum to a separate plastic vial. Refrigerate serum while awaiting shipment. Transport with a cold pack.

Stability: Refrigerated (preferred): 28 days; Frozen: 28 days; Ambient: 72 hours.

Reject Due To: Gross hemolysis, gross lipemia, gross icterus, insufficient sample volume.

Centrifuge samples and transfer 4 mL serum (2.5 mL minimum) to a separate plastic aliquot. Refrigerate serum.

Sendouts:

• Order Mayo Test: ENS2
• Interfaced: Yes [Interface: 601; Worksheet: MARF]

Stability: Refrigerated (preferred): 28 days; Frozen: 28 days; Ambient: 72 hours.

Reject Due To: Gross hemolysis, gross lipemia, gross icterus, insufficient sample volume.