Test ID: DMC2 Dementia, Autoimmune/Paraneoplastic Evaluation, Spinal Fluid
Ordering Guidance
Multiple neuroimmunology profile tests are available. For testing that is performed with each profile, see Autoimmune Neurology Antibody Matrix.
Necessary Information
Provide the following information:
-Relevant clinical information
-Ordering provider name, phone number, mailing address, and e-mail address
Specimen Required
Collection Container/Tube: Sterile vial
Specimen Volume: 4 mL
Forms
If not ordering electronically, complete, print, and send a Neurology Specialty Testing Client Test Request (T732) with the specimen.
Useful For
Investigating new onset dementia and cognitive impairment plus 1 or more of the following accompaniments using cerebrospinal fluid specimens:
-Rapid onset and progression
-Fluctuating course
-Psychiatric accompaniments (psychosis, hallucinations)
-Movement disorder (myoclonus, tremor, dyskinesias)
-Headache
-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 or more pack-years) or other cancer risk factors
-History of cancer
-Inflammatory cerebrospinal fluid
-Neuroimaging findings atypical for degenerative etiology
Profile Information
Test ID | Reporting Name | Available Separately | Always Performed |
---|---|---|---|
ADMCI | Dementia, Interpretation, CSF | No | Yes |
AMPCC | AMPA-R Ab CBA, CSF | No | Yes |
AMPHC | Amphiphysin Ab, CSF | No | Yes |
AGN1C | Anti-Glial Nuclear Ab, Type 1 | No | Yes |
ANN1C | Anti-Neuronal Nuclear Ab, Type 1 | No | Yes |
ANN2C | Anti-Neuronal Nuclear Ab, Type 2 | No | Yes |
ANN3C | Anti-Neuronal Nuclear Ab, Type 3 | No | Yes |
CS2CC | CASPR2-IgG CBA, CSF | No | Yes |
CRMC | CRMP-5-IgG, CSF | No | Yes |
DPPIC | DPPX Ab IFA, CSF | No | Yes |
GABCC | GABA-B-R Ab CBA, CSF | No | Yes |
GD65C | GAD65 Ab Assay, CSF | Yes | Yes |
GFAIC | GFAP IFA, CSF | No | Yes |
IG5IC | IgLON5 IFA, CSF | No | Yes |
LG1CC | LGI1-IgG CBA, CSF | No | Yes |
GL1IC | mGluR1 Ab IFA, CSF | No | Yes |
NCDIC | Neurochondrin IFA, CSF | No | Yes |
NIFIC | NIF IFA, CSF | No | Yes |
NMDCC | NMDA-R Ab CBA, CSF | No | Yes |
PCTRC | Purkinje Cell Cytoplasmc Ab Type Tr | No | Yes |
PCA2C | Purkinje Cell Cytoplasmic Ab Type 2 | No | Yes |
Reflex Tests
Test ID | Reporting Name | Available Separately | Always Performed |
---|---|---|---|
AGNBC | AGNA-1 Immunoblot, CSF | No | No |
AINCC | Alpha Internexin CBA, CSF | No | No |
AMPIC | AMPA-R Ab IF Titer Assay, CSF | No | No |
AMIBC | Amphiphysin Immunoblot, CSF | No | No |
AN1BC | ANNA-1 Immunoblot, CSF | No | No |
AN2BC | ANNA-2 Immunoblot, CSF | No | No |
CRMWC | CRMP-5-IgG Western Blot, CSF | Yes | No |
DPPCC | DPPX Ab CBA, CSF | No | No |
DPPTC | DPPX Ab IFA Titer, CSF | No | No |
GABIC | GABA-B-R Ab IF Titer Assay, CSF | No | No |
GFACC | GFAP CBA, CSF | No | No |
GFATC | GFAP IFA Titer, CSF | No | No |
IG5CC | IgLON5 CBA, CSF | No | No |
IG5TC | IgLON5 IFA Titer, CSF | No | No |
GL1CC | mGluR1 Ab CBA, CSF | No | No |
GL1TC | mGluR1 Ab IFA Titer, CSF | No | No |
NFHCC | NIF Heavy Chain CBA, CSF | No | No |
NIFTC | NIF IFA Titer, CSF | No | No |
NFLCC | NIF Light Chain CBA, CSF | No | No |
NMDIC | NMDA-R Ab IF Titer Assay, CSF | No | No |
PCTBC | PCA-Tr Immunoblot, CSF | No | No |
AGNTC | AGNA-1 Titer, CSF | No | No |
AN1TC | ANNA-1 Titer, CSF | No | No |
AN2TC | ANNA-2 Titer, CSF | No | No |
AN3TC | ANNA-3 Titer, CSF | No | No |
APHTC | Amphiphysin Ab Titer, CSF | No | No |
CRMTC | CRMP-5-IgG Titer, CSF | No | No |
NCDCC | Neurochondrin CBA, CSF | No | No |
NCDTC | Neurochondrin IFA Titer, CSF | No | No |
PCTTC | PCA-Tr Titer, CSF | No | No |
PC2TC | PCA-2 Titer, CSF | No | No |
Testing Algorithm
If the indirect immunofluorescence assay (IFA) pattern suggests antiglial nuclear antibody (AGNA)-1 antibody, then AGNA-1 immunoblot and AGNA-1 titer will be performed at an additional charge.
If the IFA pattern suggests antineuronal nuclear antibody type 1 (ANNA-1), then ANNA-1 immunoblot, ANNA-1 IFA titer, and ANNA-2 immunoblot will be performed at an additional charge.
If the IFA pattern suggests ANNA-2 antibody, then ANNA-2 immunoblot, ANNA-2 IFA titer, and ANNA-1 immunoblot will be performed at an additional charge.
If the IFA pattern suggests ANNA-3 antibody, then ANNA-3 titer will be performed at an additional charge.
If the IFA pattern suggests amphiphysin antibody, then amphiphysin immunoblot and amphiphysin IFA titer will be performed at an additional charge.
If the IFA pattern suggests Purkinje cell antibody type 2 (PCA-2), then PCA-2 IFA titer will be performed at an additional charge.
If the IFA pattern suggests PCA-Tr antibody, then PCA-Tr immunoblot and PCA-Tr IFA titer will be performed at an additional charge.
If client requests or if the IFA patterns suggest collapsin response-mediator protein-5 (CRMP-5)-IgG, then CRMP-5-IgG Western blot and CRMP-5-IgG IFA titer will be performed at an additional charge.
If alpha-amino-3-hydroxy-5 methyl-4-isoxazolepropionic acid (AMPA)-receptor antibody cell-binding assay (CBA) is positive, then AMPA-receptor antibody IFA titer assay will be performed at an additional charge.
If gamma-aminobutyric acid (GABA)-B-receptor antibody CBA is positive, then GABA-B-receptor antibody IFA titer assay will be performed at an additional charge.
If the IFA pattern suggests glial fibrillary acidic protein (GFAP) antibody, then GFAP IFA titer and GFAP CBA will be performed at an additional charge.
If N-methyl-D-aspartate (NMDA)-receptor antibody CBA is positive, then NMDA-receptor antibody IFA titer assay will be performed at an additional charge.
If the IFA pattern suggests dipeptidyl-peptidase-like protein-6 (DPPX) antibody, then DPPX antibody CBA and DPPX antibody IFA titer will be performed at an additional charge.
If the IFA pattern suggests metabotropic glutamate receptor 1 (mGluR1) antibody, then mGluR1 antibody CBA and mGluR1 antibody IFA titer will be performed at an additional charge.
If the IFA pattern suggests IgLON5 antibody, then IgLON5 antibody CBA and IgLON5 IFA titer will be performed at an additional charge.
If the IFA pattern suggests neuronal intermediate filament (NIF) antibody, then alpha internexin CBA, NIF heavy chain CBA, NIF light chain CBA, and NIF IFA titer will be performed at an additional charge.
If the IFA pattern suggests neurochondrin antibody, then neurochondrin antibody CBA and neurochondrin IFA titer will be performed at an additional charge.
For more information see Autoimmune/Paraneoplastic Dementia Evaluation Algorithm-Spinal Fluid.
Special Instructions
Method Name
AGN1C, AGNTC, AMPIC, AMPHC, APHTC, ANN1C, AN1TC, ANN2C, AN2TC, ANN3C, AN3TC, CRMTC, CRMC, DPPIC, DPPTC, GABIC, GFAIC, GFATC, IG5IC, IG5TC, GL1IC, GL1TC, NCDIC, NCDTC, NIFIC, NIFTC, NMDIC, PCA2C, PC2TC, PCTRC, PCTTC: Indirect Immunofluorescence Assay (IFA)
AMPCC, CS2CC, DPPCC, GABCC, GFACC, IG5CC, LG1CC, GL1CC, NCDCC, AINCC, NFLCC, NFHCC, NMDCC: Cell Binding Assay (CBA)
AGNBC, AMIBC, AN1BC, AN2BC, PCTBC: Immunoblot (IB)
CRMWC: Western Blot (WB)
GD65C: Radioimmunoassay (RIA)
Reporting Name
Dementia, Autoimm/Paraneo, CSFSpecimen Type
CSFSpecimen Minimum Volume
2 mL
Specimen Stability Information
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
CSF | Refrigerated (preferred) | 28 days | |
Frozen | 28 days | ||
Ambient | 72 hours |
Clinical Information
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 as a triad of:
-Suspicious clinical features (a subacute onset of symptoms, a rapidly progressive course, and fluctuating symptoms) and radiological findings
-Detection of cerebrospinal fluid (CSF) or serological biomarkers of autoimmunity
-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, LGI1 (leucine-rich, glioma inactivated 1) antibody was initially considered to be specific for autoimmune limbic encephalitis, but, over time, other presentations have been reported, including rapidly progressive course of cognitive decline mimicking neurodegenerative dementia.
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 CRMP-5-IgG, and subsequent testing reveals muscle acetylcholine receptor (AChR) binding antibody, the 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, although, in some circumstances, testing both serum and CSF simultaneously is pertinent. Testing of CSF is recommended for some antibodies in particular (such as NMDA-R antibody and glial fibrillary acidic protein [GFAP]-IgG) because CSF testing is both more sensitive and specific.
Reference Values
Test ID |
Reporting name |
Methodology* |
Reference value |
ADMCI |
Dementia, Interpretation, CSF |
Medical interpretation |
NA |
AMPCC |
AMPA-R Ab CBA, CSF |
CBA |
Negative |
AMPHC |
Amphiphysin Ab, CSF |
IFA |
Negative |
AGN1C |
Anti-Glial Nuclear Ab, Type 1 |
IFA |
Negative |
ANN1C |
Anti-Neuronal Nuclear Ab, Type 1 |
IFA |
Negative |
ANN2C |
Anti-Neuronal Nuclear Ab, Type 2 |
IFA |
Negative |
ANN3C |
Anti-Neuronal Nuclear Ab, Type 3 |
IFA |
Negative |
CS2CC |
CASPR2-IgG CBA, CSF |
CBA |
Negative |
CRMC |
CRMP-5-IgG, CSF |
IFA |
Negative |
DPPIC |
DPPX Ab IFA, CSF |
IFA |
Negative |
GABCC |
GABA-B-R Ab CBA, CSF |
CBA |
Negative |
GD65C |
GAD65 Ab Assay, CSF |
RIA |
≤0.02 nmol/L Reference values apply to all ages. |
GFAIC |
GFAP IFA, CSF |
IFA |
Negative |
IG5IC |
IgLON5 IFA, CSF |
IFA |
Negative |
LG1CC |
LGI1-IgG CBA, CSF |
CBA |
Negative |
NCDIC |
Neurochondrin IFA, CSF |
IFA |
Negative |
GL1IC |
mGluR1 Ab IFA, CSF |
IFA |
Negative |
NIFIC |
NIF IFA, CSF |
IFA |
Negative |
NMDCC |
NMDA-R Ab CBA, CSF |
CBA |
Negative |
PCTRC |
Purkinje Cell Cytoplasmc Ab Type Tr |
IFA |
Negative |
PCA2C |
Purkinje Cell Cytoplasmic Ab Type 2 |
IFA |
Negative |
Reflex Information:
Test ID |
Reporting name |
Methodology* |
Reference value |
AGNBC |
AGNA-1 Immunoblot, CSF |
IB |
Negative |
AGNTC |
AGNA-1 Titer, CSF |
IFA |
<1:2 |
AINCC |
Alpha Internexin CBA, CSF |
CBA |
Negative |
AMPIC |
AMPA-R Ab IF Titer Assay, CSF |
IFA |
<1:2 |
AMIBC |
Amphiphysin Immunoblot, CSF |
IB |
Negative |
AN1BC |
ANNA-1 Immunoblot, CSF |
IB |
Negative |
AN1TC |
ANNA-1 Titer, CSF |
IFA |
<1:2 |
AN2BC |
ANNA-2 Immunoblot, CSF |
IB |
Negative |
AN2TC |
ANNA-2 Titer, CSF |
IFA |
<1:2 |
AN3TC |
ANNA-3 Titer, CSF |
IFA |
<1:2 |
APHTC |
Amphiphysin Ab Titer, CSF |
IFA |
<1:2 |
CRMTC |
CRMP-5-IgG Titer, CSF |
IFA |
<1:2 |
CRMWC |
CRMP-5-IgG Western Blot, CSF |
WB |
Negative |
DPPCC |
DPPX Ab CBA, CSF |
CBA |
Negative |
DPPTC |
DPPX Ab IFA Titer, CSF |
IFA |
<1:2 |
GABIC |
GABA-B-R Ab IF Titer Assay, CSF |
IFA |
<1:2 |
GFACC |
GFAP CBA, CSF |
CBA |
Negative |
GFATC |
GFAP IFA Titer, CSF |
IFA |
<1:2 |
IG5CC |
IgLON5 CBA, CSF |
CBA |
Negative |
IG5TC |
IgLON5 IFA Titer, CSF |
IFA |
<1:2 |
GL1CC |
mGluR1 Ab CBA, CSF |
CBA |
Negative |
GL1TC |
mGluR1 Ab IFA Titer, CSF |
IFA |
<1:2 |
NCDCC |
Neurochondrin CBA, CSF |
CBA |
Negative |
NCDTC |
Neurochondrin IFA Titer, CSF |
IFA |
<1:2 |
NFHCC |
NIF Heavy Chain CBA, CSF |
CBA |
Negative |
NIFTC |
NIF IFA Titer, CSF |
IFA |
<1:2 |
NFLCC |
NIF Light Chain CBA, CSF |
CBA |
Negative |
NMDIC |
NMDA-R Ab IF Titer Assay, CSF |
IFA |
<1:2 |
PC2TC |
PCA-2 Titer, CSF |
IFA |
<1:2 |
PCTBC |
PCA-Tr Immunoblot, CSF |
IB |
Negative |
PCTTC |
PCA-Tr Titer, CSF |
IFA |
<1:2 |
*Methodology abbreviations:
Immunofluorescence assay (IFA)
Cell-binding assay (CBA)
Western blot (WB)
Radioimmunoassay (RIA)
Immunoblot (IB)
Neuron-restricted patterns of IgG staining that do not fulfill criteria for ANNA-1, ANNA-2, ANNA-3, CRMP-5-IgG, PCA-2, or PCA-Tr may be reported as "unclassified anti-neuronal IgG." Complex patterns that include nonneuronal elements may be reported as "uninterpretable."
Note: CRMP-5 titers lower than 1:2 are detectable by recombinant CRMP-5 Western blot analysis. CRMP-5 Western blot analysis will be done on request on stored spinal fluid (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
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).
Clinical Reference
1. McKeon A, Lennon VA, Pittock SJ: Immunotherapy-responsive dementias and encephalopathies. Continuum (Minneap Minn). 2010 Apr;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. 2010 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 Jul 12;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 Feb;70(2):229-234
Day(s) Performed
Profile tests: Monday through Sunday; Reflex tests: Varies
Report Available
8 to 12 daysTest Classification
This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.CPT Code Information
86255 x 19
86341
84182-AGNBC (if appropriate)
86256 AGNTC (if appropriate)
86255-AINCC (if appropriate)
86256-AMPIC (if appropriate)
84182-AMIBC (if appropriate)
84182-AN1BC (if appropriate)
86256 AN1TC (if appropriate)
84182-AN2BC (if appropriate)
86256 AN2TC (if appropriate)
86256 AN3TC (if appropriate)
86256 APHTC (if appropriate)
86256 CRMTC (if appropriate)
84182-CRMWC (if appropriate)
86255-DPPCC (if appropriate)
86256-DPPTC (if appropriate)
86256-GABIC (if appropriate)
86255-GFACC (if appropriate)
86256-GFATC (if appropriate)
86255-IG5CC (if appropriate)
86256-IG5TC (if appropriate)
86255 NCDCC (if appropriate)
86256 NCDTC (if appropriate)
86255-GL1CC (if appropriate)
86256-GL1TC (if appropriate)
86255-NFHCC (if appropriate)
86256-NIFTC (if appropriate)
86255-NFLCC (if appropriate)
86256-NMDIC (if appropriate)
86256 PC2TC (if appropriate)
84182-PCTBC (if appropriate)
86256 PCTTC (if appropriate)
LOINC Code Information
Test ID | Test Order Name | Order LOINC Value |
---|---|---|
DMC2 | Dementia, Autoimm/Paraneo, CSF | 94707-7 |
Result ID | Test Result Name | Result LOINC Value |
---|---|---|
61513 | NMDA-R Ab CBA, CSF | 93502-3 |
61514 | AMPA-R Ab CBA, CSF | 93491-9 |
61515 | GABA-B-R Ab CBA, CSF | 93426-5 |
34254 | Dementia, Interpretation, CSF | 69048-7 |
89079 | AGNA-1, CSF | 94355-5 |
5906 | Amphiphysin Ab, CSF | 94354-8 |
3852 | ANNA-1, CSF | 94356-3 |
7472 | ANNA-2, CSF | 94357-1 |
21633 | ANNA-3, CSF | 94358-9 |
21650 | CRMP-5-IgG, CSF | 94706-9 |
21632 | PCA-2, CSF | 94364-7 |
21631 | PCA-Tr, CSF | 94362-1 |
21702 | GAD65 Ab Assay, CSF | 94359-7 |
64280 | LGI1-IgG CBA, CSF | 94288-8 |
64282 | CASPR2-IgG CBA, CSF | 94286-2 |
64929 | DPPX Ab IFA, CSF | 82989-5 |
64927 | mGluR1 Ab IFA, CSF | 94361-3 |
605156 | GFAP IFA, CSF | 94360-5 |
606965 | NIF IFA, CSF | 96490-8 |
606947 | IgLON5 IFA, CSF | 96479-1 |
615866 | Neurochondrin IFA, CSF | 101451-3 |
618893 | IFA Notes | 48767-8 |
mml-neuroimmunology