Test Catalog

Test ID: DMS1    
Dementia, Autoimmune Evaluation, Serum

Useful For Suggests clinical disorders or settings where the test may be helpful

Investigating new onset dementia and cognitive impairment plus 1 or more of the following:

-Rapid onset and progression

-Fluctuating course

-Psychiatric accompaniments (psychosis, hallucinations)

-Movement disorder (myoclonus, tremor, dyskinesias)


-Autoimmune stigmata (personal history or family history or signs of diabetes mellitus, thyroid disorder, vitiligo, poliosis [premature graying], myasthenia gravis, rheumatoid arthritis, systemic lupus erythematosus)

-Smoking history (20+ pack years) or other cancer risk factors

-History of cancer

-Inflammatory cerebral spinal fluid

-Neuroimaging findings atypical for degenerative etiology

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

If indirect immunofluorescence assay (IFA) (ANNA-1, ANNA-2, ANNA-3, PCA-2, PCA-Tr, Amphiphysin, CRMP-5-IgG, AGNA-1)) is indeterminate, paraneoplastic autoantibody Western blot is performed at an additional charge.


If client requests or if IFA patterns suggest CRMP-5-IgG, CRMP-5-IgG Western blot is performed at an additional charge.


If IFA patterns suggest amphiphysin antibody, amphiphysin Western blot is performed at an additional charge.


If IFA pattern suggest NMO/AQP4-IgG, NMO/AQP4-IgG FACS is performed at an additional charge.


If NMO/AQP4-IgG FACS screen assay requires further investigation, then NMO/AQP4-IgG FACS titration assay is performed at an additional charge.


If IFA pattern suggest AMPA-Receptor antibody and AMPA-Receptor antibody CBA is positive, AMPA-Receptor antibody IF titer assay is performed at an additional charge.


If IFA pattern suggest GABA-B-Receptor antibody and GABA-B-R Receptor Ab antibody is positive, GABA-B-R Receptor Ab antibody IF titer assay is performed at an additional charge.


If IFA pattern suggest NMDA-Receptor antibody and NMDA-Receptor Ab antibody CBA is positive, NMDA-Receptor Ab antibody IF titer assay is performed at an additional charge.


If IFA patterns suggest PCA-1, Purkinje Cell Cytoplasmic antibody Type 1 assay is performed at an additional charge.


See Dementia Autoimmune Evaluation Algorithm, Serum in Special Instructions

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

The rapid identification of subacute cognitive decline as autoimmune dementia facilitates optimum treatment with immunotherapy and an expedited search for a limited stage of cancer in some patients. Traditionally, neurologists have been reluctant to consider a diagnosis of an autoimmune cognitive disorder in the absence of delirium. However, some recent case series and clinical-serologic observations have suggested a growing appreciation for autoimmune neurologic disorders presenting with features of a rapidly progressive dementia rather than delirium. These disorders can affect all age groups.


Unfortunately, these potentially reversible conditions may be misdiagnosed as being progressive neurodegenerative (currently irreversible) disorders, with devastating consequences for the patient. In the evaluation of a patient with cognitive decline, clinicians should consider the possibility of an autoimmune etiology on their list of differential diagnoses. The importance of not overlooking this possibility rests in the experience that these patients have a potentially immunotherapy responsive, reversible disorder. The development and widespread availability of neural antibody marker testing has changed this perspective so that other presenting symptoms such as personality change, executive dysfunction, and psychiatric symptoms are increasingly recognized in an autoimmune context.


Clues that are helpful in identifying patients with an autoimmune dementia can be summarized within a triad of: 1) suspicious clinical features (a subacute onset of symptoms, a rapidly progressive course, and fluctuating symptoms) and radiological findings, 2) the detection of cerebral spinal fluid (CSF) or serological biomarkers of autoimmunity and 3) a response to immunotherapy.


Detection of neural autoantibodies in serum or CSF serves 2 purposes; to inform the physician of a likely autoimmune etiology and to raise suspicion for a paraneoplastic cause. The neurological associations of neural autoantibodies tend to be diverse and multifocal, although certain syndromic associations may apply. For example, neuronal voltage-gated potassium channel (VGKC) antibodies were initially considered to be specific for autoimmune limbic encephalitis or disorders of peripheral nervous hyperexcitability, but over time other presentations have been reported, including a rapidly progressive course of cognitive decline mimicking frontotemporal dementia and Creutzfeldt-Jakob disease.


Since neurological presentations are often multifocal and diverse, comprehensive antibody testing is usually more informative than testing for 1 or 2 selected antibodies. Some of the antibodies are highly predictive of an unsuspected underlying cancer. For example; small-cell lung carcinoma (antineuronal nuclear antibody-type 1, ANNA-1; collapsin response-mediator protein-5 neuronal, CRMP-5-IgG), ovarian teratoma (N-methyl-D-aspartate receptor, NMDA-R), and thymoma (CRMP-5 IgG). Also, a profile of seropositivity for multiple autoantibodies may be informative for cancer type. For example, in a patient presenting with a rapidly progressive dementia who has muscle acetylcholine receptor (AChR) binding, alpha 3 ganglionic AChR, and CRMP 5 IgG, those findings should raise a high suspicion for thymoma. If an associated tumor is found, its resection or ablation optimizes the neurological outcome.


Antibody testing on CSF is additionally helpful particularly when serum testing is negative. However, simultaneous testing of serum and CSF is recommended for NMDA-R antibody, because CSF is usually more informative.

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.


Antineuronal Nuclear Ab, Type 1 (ANNA-1)


Antineuronal Nuclear Ab, Type 2 (ANNA-2)


Antineuronal Nuclear Ab, Type 3 (ANNA-3)


Anti-Glial/Neuronal Nuclear Ab, Type 1 (AGNA-1)




Purkinje Cell Cytoplasmic Ab, Type1 (PCA-1)


Purkinje Cell Cytoplasmic Ab, Type 2 (PCA-2)


Purkinje Cell Cytoplasmic Ab, Type Tr (PCA-Tr)


Amphiphysin Antibody






Paraneoplastic Western Blot


CRMP-5-IgG Western Blot


Amphiphysin Western Blot




Glutamic Acid Decarboxylase (GAD65) Antibody

< or =0.02 nmol/L



N-Type Calcium Channel Antibody

< or =0.03 nmol/L

P/Q-Type Calcium Channel Antibody

< or =0.02 nmol/L

AChR Ganglionic Neuronal Antibody

< or =0.02 nmol/L

Neuronal VGKC Autoantibody

< or =0.02 nmol/L



ACh Receptor (Muscle) Binding Antibody

< or =0.02 nmol/L


N-Methyl-D-aspartate receptor (NMDA-R) CBA


IFA: <1:120

2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl) propanoic acid receptor (AMPA-R) CBA


IFA: <1:120

Gamma-Amino Butyric acid-type B receptor (GABA-B-R) CBA


IFA: <1:120

Neuromyelitis Optica (NMO)/Aquaporin-4-IgG FACS Assay


LGI1-IgG CBA: Negative

CASPR2-IgG CBA: Negative

Interpretation Provides information to assist in interpretation of the test results

Antibodies specific for neuronal, glial, or muscle proteins are valuable serological markers of autoimmune epilepsy and of a patient's immune response to cancer. These autoantibodies are not found in healthy subjects, and are usually accompanied by subacute neurological symptoms and signs. It is not uncommon for more than 1 of the following autoantibodies to be detected in patients with autoimmune dementia:

-Plasma membrane antibodies (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). These autoantibodies are all potential effectors of dysfunction.

-Neuronal nuclear autoantibody, type 1 (ANNA-1) or type 3 (ANNA-3).

-Neuronal or muscle cytoplasmic antibodies (amphiphysin, Purkinje cell antibody-type 2 [PCA-2], collapsin response-mediator protein-5 neuronal [CRMP-5-IgG], or glutamic acid decarboxylase [GAD65] antibody).

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Negative results do not exclude autoimmune dementia or cancer.


This test does not detect Ma1 or Ma2 antibodies (alias: MaTa). Ma2 antibody has been described in patients with brainstem and limbic encephalitis in the context of testicular germ cell neoplasms. Scrotal ultrasound is advisable in men who present with unexplained subacute encephalitis.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. McKeon A, Lennon, VA, Pittock, SJ: Immunotherapy Responsive Dementias and Encephalopathies. Continuum Lifelong Learning 2010;16(2):80-101

2. Flanagan EP, McKeon A, Lennon VA, et al: Autoimmune dementia: clinical course and predictors of immunotherapy response. Mayo Clin Proc Oct;85(10):881-897

3. Geschwind MD, Tan KM, Lennon VA, et al: Voltage-gated potassium channel autoimmunity mimicking Creutzfeldt-Jakob disease. Arch Neurol 2008 Oct;65(10):1341-1346

4. Lancaster E, Martinez-Hernandez E, Dalmau J: Encephalitis and antibodies to synaptic and neuronal cell surface proteins. Neurology 2011;77(2):179-189

5. Klein CJ, Lennon VA, Aston PA, et al: Insights from LGI1 and CASPR2 potassium channel complex autoantibody subtyping. JAMA Neurol 2013;70(2):229-234

Special Instructions Library of PDFs including pertinent information and forms related to the test