Autoimmune Encephalopathy and Dementia Panel, Serum and CSF

Content Review: May 2023 Last Update:

Autoimmune encephalopathy and autoimmune dementia are rare but important reversible causes of cognitive impairment and decline.   Recognition of autoimmune causes of neurologic symptoms and detection of antineural antibodies may help to establish a diagnosis, support treatment decisions, aid with prognostication, serve as a prerequisite for enrollment in clinical trials, and guide the search for an associated malignancy.

Disease Overview

Autoimmune encephalopathy and autoimmune dementia may develop in the context of paraneoplastic neurologic syndromes or postinfectious syndromes but are most often idiopathic. A diagnosis of possible autoimmune encephalitis should be considered if there is a subacute onset or rapid progression (in <3 months) of short-term memory loss, altered level of consciousness, lethargy, personality change, or psychiatric symptoms as well as either new focal central nervous system (CNS) findings, seizures without another explanation, cerebrospinal fluid (CSF) pleocytosis, or magnetic resonance imaging (MRI) features suggestive of encephalitis, with reasonable exclusion of alternative causes.  Although antibody testing is not required for the diagnosis of possible autoimmune encephalitis, it plays an important role in increasing the level of certainty of the diagnosis to probable or definite. The Antibody Prevalence in Epilepsy and Encephalopathy (APE2) score can be used when considering autoimmune causes of encephalopathy and dementia to determine the likelihood that antineural antibodies will be present. 

For more information about laboratory testing for autoimmune neurologic diseases, refer to the ARUP Consult Autoimmune Neurologic Diseases - Antineural Antibody Testing topic.

Test Description

ARUP’s serum and CSF Autoimmune Encephalopathy/Dementia Panels can be used for the evaluation of patients with new, acute- to subacute-onset encephalopathy, dementia, or cognitive impairment. Testing for the presence of antineural antibodies in both serum and CSF may improve diagnostic yield. 

These phenotype-targeted panels test for the presence of antibodies associated with autoimmune encephalopathy and autoimmune dementia. Clinical phenotypes for specific antineural antibody-associated syndromes often overlap, and phenotype-specific panels allow for rapid identification of associated antibodies, which may have implications for treatment, prognosis, cancer screening, and clinical trial enrollment.  Other panels may be more appropriate, depending on the patient’s clinical phenotype:

ARUP Phenotype-Specific Panels to Consider for Autoimmune Neurologic Disease
ARUP Panel
Test Code
Serum CSF

Autoimmune Epilepsy Panel

3006204

3006205

Autoimmune Movement Disorder Panel

3006206

3006207

Autoimmune Pediatric CNS Disorders Panel

3006210

3006211

Regardless of the panel chosen, order only one panel for serum and/or one panel for CSF; many antineural antibodies are redundant between these panels, and choosing based on the predominant phenotype will provide the most meaningful results. To compare these panels and the antibodies included, refer to ARUP Autoimmune Neurology Panel Components.

Testing for individual antibodies is also available separately.

Antibodies Tested and Methodology

Autoimmune Encephalopathy/Dementia Panel, Serum (3006201) and CSF (3006202): Antibodies Tested and Methodology
Autoantibody Markers Methodology
Individual Autoantibody Test Code
Serum CSF

AMPAR Ab, IgG

CBA-IFA, reflex titer

3001260

3001257

Amphiphysin Ab, IgG

IB

2008893

3004510

ANNA-1 (Hu)

IFA, reflex IB, reflex titer

2007961

2010841

ANNA-2 (Ri)

IFA, reflex IB, reflex titer

2007961

2010841

CASPR2 Ab, IgG

CBA-IFA, reflex titer

2009452

3001986

CV2 (CRMP-5) Ab, IgG

CBA-IFA, reflex titer

3016999

3017001

DPPX Ab, IgG

CBA-IFA, reflex titer

3004359

3004512

GABA-BR Ab, IgG

CBA-IFA, reflex titer

3001270

3001267

GAD65 Ab

ELISA

2001771

3002788

IgLON5 Ab, IgG

CBA-IFA, reflex titer

3006018

3006013

LGI1 Ab, IgG

CBA-IFA, reflex titer

2009456

3001992

mGluR1 Ab, IgG

CBA-IFA, reflex titer

3006044

3006039

NMDAR Ab, IgG

CBA-IFA, reflex titer

2004221

2005164

PCCA-1 (Yo)

IFA, reflex IB, reflex titer

2007961

2010841

PCCA-Tr/DNER

IFA, reflex IB, reflex titer

2007961

2010841

SOX1 (AGNA) Ab, IgG

IB

3002885

3002886

Ab, antibody; AGNA, antiglial nuclear antibody; AMPAR, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor; ANNA, antineuronal nuclear antibody type 1; ANNA-2, antineuronal nuclear antibody type 2; CASPR2, contactin-associated protein 2; CBA, cell-binding assay/cell-based assay; CRMP-5, collapsin response-mediator protein 5; DNER, Delta/notch-like epidermal growth factor-related receptor; DPPX, dipeptidyl-aminopeptidase-like protein 6; ELISA, enzyme-linked immunosorbent assay; GABA-BR, gamma-aminobutyric acid receptor, type B; GAD65, glutamic acid decarboxylase 65-kd isoform; IB, immunoblot; IFA, indirect immunofluorescence assay; IgG, immunoglobulin G; IgLON5, IgLON family member 5; LGl1, leucine-rich, glioma-inactivated protein 1; mGluR1, metabotropic glutamate receptor 1; NMDAR, N-methyl-D-aspartate receptor; PCCA-1, Purkinje cell cytoplasmic antibody type 1; PCCA-Tr, Purkinje cell cytoplasmic antibody type Tr; SOX1, SRY-box transcription factor 1

Reflex Patterns

Autoimmune Encephalopathy/Dementia Panel, Serum (3006201) and CSF (3006202): Reflex Patterns

Reflex pattern for Autoimmune Encephalopathy/Dementia Panels

Limitations

These panels do not include every antibody that has been associated with autoimmune dementia or encephalopathy:

  • ANNA-3 and PCCA-2 are not included because they are extremely rare (present in approximately 0.0001% of specimens submitted for evaluation using a paraneoplastic antibody panel), and commercial assays to confirm the specificity of these antibodies are not currently available. 
  • Glial fibrillary acidic protein (GFAP), neuronal intermediate filament (NIF) and its associated reflexes (NIF heavy and light chain, alpha internexin), neurochondrin, and septin 7 are not included because they have been only recently identified and their prevalence is currently not well established.
    • GFAP has been reported in 0.17% of samples screened, often co-occurring with other antineural antibodies. 
    • NIF has been reported in 0.014% of samples screened; NIF heavy and light chain and alpha internexin were reflexed in samples which were positive for NIF to further identify the associated antibody. 
    • Neurochondrin has been reported in 0.002% of samples tested. 
    • Septin 7 has been reported in 0.002% of samples screened. 
  • As testing for newly described antibodies becomes available and their clinical relevance is established, these panels will evolve to reflect these discoveries.

Test Interpretation

Results

Results must be interpreted in the clinical context of the individual patient; test results (positive or negative) should not supersede clinical judgment.

Autoimmune Encephalopathy/Dementia Panel, Serum (3006201) and CSF (3006202): Results Interpretation
Result Interpretation

Positive for ≥1 autoantibodies

Autoantibody(ies) detected

Supports a clinical diagnosis of an autoimmune encephalopathy or autoimmune dementia

Consider a focused search for malignancy based on antibody-tumor associations

Negative

No autoantibodies detected

A diagnosis of an autoimmune encephalopathy or autoimmune dementia is not excluded

References