Autoimmune Encephalitis Panel, Serum (Sendout)

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General Information

Lab Name
Autoimmune Encephalitis Panel, Serum (Sendout)
Lab Code
RSAENP
Epic Ordering
Autoimmune Encephalitis Panel, Serum (Sendout)
External Test Id
ENS2
Description

Useful For:

  • Evaluating new onset encephalopathy (noninfectious or metabolic) comprising confusional states, psychosis, delirium, memory loss, hallucinations, movement disorders, sensory or motor complaints, seizures, dyssomnias, ataxias, nausea, vomiting, inappropriate antidiuresis, coma, dysautonomias, or hypoventilation using serum specimens.
  • Evaluating limbic encephalitis (noninfectious)
  • Directing a focused search for cancer
  • Investigating encephalopathy appearing during or after cancer therapy and not explainable by metastasis or drug effect

The following accompaniments should increase of suspicion for autoimmune encephalopathy:

  • Headache
  • 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 or more pack-years) or other cancer risk factors
  • Inflammatory cerebral spinal fluid (or isolated protein elevation)
  • Neuroimaging signs suggesting inflammation

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.

Ordering Guidance: Mayo's APE² Score card linked below 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.

References
  • Graus F, Titulaer MJ, Balu R, Benseler S, Bien CG, Cellucci T, Cortese I, Dale RC, Gelfand JM, Geschwind M, Glaser CA, Honnorat J, Höftberger R, Iizuka T, Irani SR, Lancaster E, Leypoldt F, Prüss H, Rae-Grant A, Reindl M, Rosenfeld MR, Rostásy K, Saiz A, Venkatesan A, Vincent A, Wandinger KP, Waters P, and Dalmau J. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 2016, 15:391-404. 26906964
  • Abboud H, Probasco JC, Irani S, Ances B, Benavides DR, Bradshaw M, Christo PP, Dale RC, Fernandez-Fournier M, Flanagan EP, Gadoth A, George P, Grebenciucova E, Jammoul A, Lee ST, Li Y, Matiello M, Morse AM, Rae-Grant A, Rojas G, Rossman I, Schmitt S, Venkatesan A, Vernino S, Pittock SJ, Titulaer MJ; Autoimmune Encephalitis Alliance Clinicians Network. Autoimmune encephalitis: proposed best practice recommendations for diagnosis and acute management. J Neurol Neurosurg Psychiatry. 2021 Jul;92(7):757-768. doi: 10.1136/jnnp-2020-325300. Epub 2021 Mar 1. PMID: 33649022; PMCID: PMC8223680.
  • Dalmau J, Graus F. Antibody-Mediated Encephalitis. N Engl J Med. 2018 Mar 1;378(9):840-851. doi: 10.1056/NEJMra1708712. PMID: 29490181.
  • Dubey D, Kothapalli N, McKeon A, Flanagan EP, Lennon VA, Klein CJ, Britton JW, So E, Boeve BF, Tillema JM, Sadjadi R, Pittock SJ. Predictors of neural-specific autoantibodies and immunotherapy response in patients with cognitive dysfunction. J Neuroimmunol. 2018 Oct 15;323:62-72. doi: 10.1016/j.jneuroim.2018.07.009. Epub 2018 Jul 25. PMID: 30196836.
  • Mayo Clinical and Interpretive Information: Encephalopathy, Autoimmune/Paraneoplastic Evaluation, Serum
Synonyms
Encephalitis, Encephalopathy, ENS2, Limbic encephalitis
Components

Interpretation

Method

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, DPPX Ab IFA, GFAP, IgLON5, mGluR1 Ab, Neurochondrin, NIF, Purkinje Cell Cytoplasmic Ab Type 1, Purkinje Cell Cytoplasmic Ab Type 2, Purkinje Cell Cytoplasmic Ab Type Tr, Septin-7.

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

Radioimmunoassay (RIA): GAD65 Ab Assay

Reference Range
See individual components
Ref. Range Notes

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

Interferences and Limitations

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.

References
  • Graus F, Titulaer MJ, Balu R, Benseler S, Bien CG, Cellucci T, Cortese I, Dale RC, Gelfand JM, Geschwind M, Glaser CA, Honnorat J, Höftberger R, Iizuka T, Irani SR, Lancaster E, Leypoldt F, Prüss H, Rae-Grant A, Reindl M, Rosenfeld MR, Rostásy K, Saiz A, Venkatesan A, Vincent A, Wandinger KP, Waters P, and Dalmau J. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 2016, 15:391-404. 26906964
  • Abboud H, Probasco JC, Irani S, Ances B, Benavides DR, Bradshaw M, Christo PP, Dale RC, Fernandez-Fournier M, Flanagan EP, Gadoth A, George P, Grebenciucova E, Jammoul A, Lee ST, Li Y, Matiello M, Morse AM, Rae-Grant A, Rojas G, Rossman I, Schmitt S, Venkatesan A, Vernino S, Pittock SJ, Titulaer MJ; Autoimmune Encephalitis Alliance Clinicians Network. Autoimmune encephalitis: proposed best practice recommendations for diagnosis and acute management. J Neurol Neurosurg Psychiatry. 2021 Jul;92(7):757-768. doi: 10.1136/jnnp-2020-325300. Epub 2021 Mar 1. PMID: 33649022; PMCID: PMC8223680.
  • Dalmau J, Graus F. Antibody-Mediated Encephalitis. N Engl J Med. 2018 Mar 1;378(9):840-851. doi: 10.1056/NEJMra1708712. PMID: 29490181.
  • Dubey D, Kothapalli N, McKeon A, Flanagan EP, Lennon VA, Klein CJ, Britton JW, So E, Boeve BF, Tillema JM, Sadjadi R, Pittock SJ. Predictors of neural-specific autoantibodies and immunotherapy response in patients with cognitive dysfunction. J Neuroimmunol. 2018 Oct 15;323:62-72. doi: 10.1016/j.jneuroim.2018.07.009. Epub 2018 Jul 25. PMID: 30196836.
  • Mayo Clinical and Interpretive Information: Encephalopathy, Autoimmune/Paraneoplastic Evaluation, Serum
Guidelines

Ordering & Collection

Specimen Type
Blood
Collection

12 mL blood in RED TOP or GOLD SST tubes

Approval Required
Orders from UW Medicine Neurology Clinics are pre-approved. For all other orders, Laboratory Medicine Resident (LMR) approval is required.
Handling Instructions

Outside Laboratories: Centrifuge samples and transfer serum to a separate plastic vial. Refrigerate serum.

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

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

Quantity
requested: 4 mL serum
minimum: 2.5 mL serum

Processing

Processing

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.

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

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

Performance

LIS Dept Code
Sendouts Mayo Lab (RF) (MARF)
Performing Location(s)
Sendout Mayo Clinic Laboratories
800-533-1710

200 First Street Southwest
Rochester, MN 55901
Frequency
Performed: Varies. Report available: 10-13 days.
Available STAT?
No

Billing & Coding

CPT codes
86255x21, 86341
LOINC
94697-0
Interfaced Order Code
UOW4912