Autoimmune encephalopathy
Diagnosing an increasingly recognized condition
Many cases of encephalopathy previously considered infectious are now recognized to have an autoimmune cause. In fact, based on a recent Mayo Clinic study, autoimmune encephalitis was found to be as common as infectious encephalitis.1 Our full suite of encephalopathy testing includes comprehensive evaluations, targeted antibody testing, and complementary assays to pinpoint causes and facilitate personalized therapy selection.
Autoimmune encephalopathy Test menu
Encephalopathy
Our comprehensive autoimmune encephalopathy evaluation is part of an evolving approach to testing for autoimmune neurological disorders using phenotype-specific evaluations that include multiple antibodies known for their disease association.
Key testing
- ENC2 | Encephalopathy, Autoimmune/Paraneoplastic Evaluation, Spinal Fluid
- ENS2 | Encephalopathy, Autoimmune/Paraneoplastic Evaluation, Serum
Advantages
- Evaluates for 20 antibodies with known association to autoimmune encephalopathy.
- Facilitates diagnosis of autoimmune causes of new onset encephalopathy.
- Evaluates for encephalopathy appearing during or after cancer therapy that is not explainable by metastasis or drug effect.
- Results direct a focused search for cancer.
Infectious encephalopathy testing
Infectious causes of encephalitis can be equally devasting and must be ruled out to confidently prescribe treatment.
Highlights
Anastasia Zekeridou, M.D., Ph.D., explains how Mayo Clinic Laboratories' updated panels and methodology boost the accuracy and efficiency of testing for three autoimmune neurology biomarkers. Early diagnosis is key to managing debilitating conditions associated with these antibodies.
Divyanshu Dubey, M.B.B.S., explains how Mayo Clinic Laboratories' unique PDE10A and TRIM46 tests facilitate the management of central nervous system disorders triggered by cancers. Early diagnosis and treatment are important for managing disabling neurological symptoms and malignancy.
In this “Hot Topic,” Divyanshu Dubey, M.B.B.S., associate professor of laboratory medicine and pathology and neurology at Mayo Clinic, discusses various clinical and paraclinical features of autoimmune encephalitis, autoimmune seizures, and epilepsy.
Sean Pittock, M.D., explains how Mayo Clinic Laboratories' novel Ma2 test aids diagnosis of autoimmune neurology disorders that are often caused by underlying cancer. Rapid diagnosis is key to preventing significant disability and disease.
In this month's "Hot Topic," Eoin Flanagan, M.B., B. Ch., discusses the important issue of autoimmune encephalitis misdiagnosis and identifies red flags that be useful in clinical practice to suggest alternative diagnoses and highlight antibodies that sometimes cause confusion.
Mayo Clinic Laboratories’ comprehensive approach to targeted antibody testing played a crucial and lifesaving role in moving Sheila Lewis to recovery from autoimmune encephalitis.
In this month’s “Hot Topic,” Andrew McKeon, M.B., B.Ch., M.D., reviews the use of neurological phenotype-based evaluations, the move away from the paraneoplastic evaluation, and upcoming changes to test profiles.
For people with encephalitis, rapid treatment of their acute brain inflammation is critical for avoiding devastating physical and cognitive deficits. But appropriate treatment requires identifying the culprit causing the symptoms.
Encephalitis caused by the immune system attacking the brain is similar in frequency to encephalitis from infections, Mayo Clinic researchers report in Annals of Neurology.
Greg Widseth was suddenly hit by a rare disease that prompted his immune system to attack his brain cells, resulting in as many as 60 seizures a day. Special blood and spinal fluid tests developed by Mayo Medical Laboratories confirmed that Widseth had antibodies known to target certain brain cells.
GABA-A RECEPTOR ANTIBODIES
Our cell-based GABA-A receptor antibody test is recommended — in conjunction with other autoimmune neurology profiles — for patients who present with encephalopathy with seizures. These patients also typically have multifocal large cerebral temporal and extra-temporal T2 signal abnormalities without enhancement. GABA-A receptor antibodies are biomarkers of autoimmune encephalopathy, which may occur at any age and disproportionately affects children. GABA-A receptor antibodies are the third most common neuronal biomarker in children, behind only NMDA receptor and MOG antibodies. Because disease associated with the GABA-A receptor antibody is responsive to immunotherapy if treated early, accurate and timely testing is critical.
Key testing
- GBACC | Gamma-Amino Butyric Acid Type A (GABA-A) Receptor Antibody by Cell Binding Assay, Spinal Fluid
- GBACS | Gamma-Amino Butyric Acid Type A (GABA-A) Receptor Antibody by Cell Binding Assay, Serum
Advantages
- Specific phenotype (88% of patients have refractory seizures).
- Evaluating GABA-A receptor improves diagnostic sensitivity thereby increasing physician confidence.
- Provides reliable confirmation of GABA-A receptor-associated disease without the need for reflex testing.
- 75% of GABA-A receptor-positive patients had a partial or complete recovery with proper treatment.4
- Direct a search for cancer when appropriate (thymoma).
Additional testing
Can be ordered as a standalone test in addition to the autoimmune encephalopathy, autoimmune epilepsy, or pediatric CNS autoimmune evaluations in patients who present with encephalopathy with seizures.
- EPC2 | Epilepsy, Autoimmune/Paraneoplastic Evaluation, Spinal Fluid
- EPS2 | Epilepsy, Autoimmune/Paraneoplastic Evaluation, Serum
Highlights
JoAnne Michael’s symptoms started with dizziness and forgetfulness before down spiraling into severe confusion, crying jags, and brain seizures. ER doctors at her local hospital initially thought she was on drugs. JoAnne, terrified, wondered if she was dying. Luckily, she had a guardian angel by her side: her mother, a retired nurse practitioner, who took her to Mayo Clinic, where the clinical experience and expertise of neurologist Andrew McKeon, M.B., B.Ch., M.D., helped give her a diagnosis and hope for a journey back to health.
Antibody against the GABA-A receptor is a biomarker of autoimmune encephalopathy that occurs across the lifespan, and disproportionately affects children. In this test-specific episode of the "Answers From the Lab" podcast, Andrew McKeon, M.B., B.Ch., M.D., explains how Mayo Clinic Laboratories' GABA-A receptor antibody assay aids diagnosis of this serious but treatable condition.
Kelch-like protein 11
The groundbreaking discovery that testicular cancer-associated paraneoplastic encephalitis is caused by Kelch-like protein 11 (KLHL11) autoantibodies — by a team of researchers that included Mayo Clinic scientists — paved the way for development of the world’s first evidence-based test to confirm KLHL11 antibodies. The test first screens patients for KLHL11 proteins through a mechanized, cell-based assay that uses cutting-edge, slide-scanner technology, then employs tissue immunofluorescence to confirm presence of the protein, which exudes a unique "sparkles" pattern.
Testicular cancer-associated paraneoplastic encephalitis, which is associated with testicular cancer in 70% of cases, is often misdiagnosed due to neurological syndrome symptoms preceding tumor detection. Early and accurate diagnosis of this syndrome is critical for disease stabilization and possible reversal.
Key testing
- K11CC | Kelch-Like Protein 11 Antibody, Cell Binding Assay, Spinal Fluid
- K11CS | Kelch-Like Protein 11 Antibody, Cell Binding Assay, Serum
Advantages
- Uses a mechanized, cell-based assay to first screen patients. If positive, testing reflexes to confirmatory, tissue immunofluorescence.
- Positive results enable specific treatment protocols, such as cancer treatments and immunosuppressive therapies, to manage and treat the disease.
Highlights
While Gregor Heinrich never could have imagined that testicular cancer was related to his problems with his vision and gait, learning he was positive for KLHL11 protein biomarkers meant he could receive treatment for both the cancer and the illness behind it.
The discovery of Kelch like protein 11 (KLHL11) IgG as a specific biomarker of neurological autoimmunity associated testicular germ cell tumor.
Divyanshu (Div) Dubey, M.B.B.S., explains how Mayo Clinic Labs’ new Kelch-11 antibody test — the first in the world — can confirm diagnosis, guide treatment, and improve outcomes in patients affected by testicular cancer-associated paraneoplastic encephalitis.
Mayo Clinic Laboratories has launched a first-in-the-U.S. autoimmune test of the Kelchlike protein 11 antibody, or KLHL11, which is used to detect autoimmune disease associated with testicular cancer.
Using advanced technology, scientists at Chan Zuckerberg (CZ) Biohub, Mayo Clinic and University of California, San Francisco (UCSF), have discovered an autoimmune disease that appears to affect men with testicular cancer.
Ma-2 antibody-associated encephalitis
We have optimized Ma2 antibody detection through the development of an innovative, enzyme-linked immunosorbent assay (ELISA). Positive test results can facilitate aggressive immunosuppressive therapies to combat the destructive immune response and help direct a search for an unidentified cancer, present in between 70% and 80% of cases, driving the disease process. Treatment of the cancer can further suppress the antibody response, with the combined therapies slowing the disease progress and potentially reversing symptoms.
Key testing
Advantages
- Uses ELISA to detect Ma2 antibodies.
- Offers increased sensitivity for improved antibody detection.
- Helps direct search for associated cancers.
- Facilitates treatment selection.
Additional testing
Ma2 testing used in conjunction with autoimmune/paraneoplastic encephalopathy and movement disorder panel evaluations provides the most comprehensive, up-to-date coverage of autoimmune/paraneoplastic antibodies available, equipping providers with assurance that nothing was missed. Because 32% of Ma2 patients present with excessive daytime sleepiness, assessing for the neuropeptide orexin can assist in confirming diagnosis.
- MDC2 | Movement Disorder, Autoimmune/Paraneoplastic Evaluation, Spinal Fluid
- MDS2 | Movement Disorder, Autoimmune/Paraneoplastic Evaluation, Serum
- ORXNA | Orexin-A/Hypocretin-1, Spinal Fluid
Highlights
Anastasia Zekeridou, M.D., Ph.D., explains how Mayo Clinic Laboratories' updated panels and methodology boost the accuracy and efficiency of testing for three autoimmune neurology biomarkers. Early diagnosis is key to managing debilitating conditions associated with these antibodies.
Divyanshu Dubey, M.B.B.S., explains how Mayo Clinic Laboratories' unique PDE10A and TRIM46 tests facilitate the management of central nervous system disorders triggered by cancers. Early diagnosis and treatment are important for managing disabling neurological symptoms and malignancy.
Sean Pittock, M.D., explains how Mayo Clinic Laboratories' novel Ma2 test aids diagnosis of autoimmune neurology disorders that are often caused by underlying cancer. Rapid diagnosis is key to preventing significant disability and disease.
References
- Dubey, D., Pittock, S.J., Kelly, C.R., et al. Autoimmune encephalitis epidemiology and a comparison to infectious encephalitis. Ann Neurol. 83: 166-177. https://doi.org/10.1002/ana.25131
- Mandel-Brehm C, Dubey D, Kryzer TJ, et al. Kelch-like Protein 11 Antibodies in Seminoma-Associated Paraneoplastic Encephalitis. N Engl J Med. 2019; 381:47-54.
- Dubey D, Wilson MR, Clarkson B, et al. Expanded Clinical Phenotype, Oncological Associations, and Immunopathologic Insights of Paraneoplastic Kelch-like Protein-11 Encephalitis. JAMA Neurol. 2020 Aug 3; 77(11):1-10. Dalmau J, Graus F, Villarejo A, et al. Clinical analysis of anti-Ma2-associated encephalitis. Brain. 2004;127(Pt 8):1831-1844. doi:10.1093/brain/awh203.
- O'Connor K, Waters P, Komorowski L, et al. GABAA receptor autoimmunity: A multicenter experience. Neurol Neuroimmunol Neuroinflamm. 2019;6(3):e552. Published 2019 Apr 4. doi:10.1212/NXI.0000000000000552
- Flanagan EP, Dubey D, Pittock SJ, et al. Autoimmune encephalitis epidemiology and a comparison to infectious encephalitis. Ann Neurol. 2018 Jan;83(1):166-177.