Autoimmune Encephalopathy and Dementia Panel, Serum and CSF

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:

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 the ARUP Antineural Antibody Testing for Autoimmune Neurologic Disease page.

Testing for individual antibodies is also available separately.

Antibodies Tested and Methodology

Reflex Patterns

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

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.