Autoimmune Encephalitis laboratory findings
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Julinka Auta Fernandes
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Autoimmune Encephalitis Microchapters |
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Differentiating Autoimmune Encephalitis from Other Conditions |
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Diagnosis |
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Treatment |
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Case Studies |
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Autoimmune Encephalitis On the Web |
Overview
Laboratory findings in autoimmune encephalitis may include inflammatory cerebrospinal fluid (CSF), evidence of intrathecal immunoglobulin G (IgG) synthesis, or a clinically relevant neural antibody. Routine blood and CSF results can be normal. No single routine laboratory pattern establishes or excludes every form of autoimmune encephalitis.[1]
Laboratory investigations support the clinical diagnosis, identify antibody-associated subtypes, and exclude infectious, metabolic, systemic inflammatory, and neoplastic mimics. Results must be interpreted with the clinical syndrome and the methods used.[2]
Laboratory Findings
Cerebrospinal Fluid Findings
Autoimmune encephalitis may produce the following CSF abnormalities. Their frequency varies substantially between subtypes, and none is individually specific for autoimmunity.[1]
| Test | Potential finding | Interpretation |
|---|---|---|
| Cell count and differential | Mild or moderate pleocytosis, often predominantly lymphocytic; counts can also be normal. | Supports inflammation but occurs in infectious and other inflammatory conditions. Adult diagnostic criteria use >5 white blood cells/mm³ as a supportive threshold.[3] |
| Total protein | May be elevated or normal. | An isolated protein elevation is nonspecific and does not establish autoimmune encephalitis. |
| Glucose, interpreted with serum glucose | Usually preserved. | Reduced CSF glucose warrants investigation of infection, malignancy, and other inflammatory causes. It can also occur in selected autoimmune disorders, including glial fibrillary acidic protein astrocytopathy. |
| Oligoclonal bands | CSF-restricted bands may be present. | Paired serum and CSF analysis helps distinguish intrathecal synthesis from a systemic antibody pattern. |
| IgG index | May be elevated. | Supports intrathecal IgG synthesis but is not specific for autoimmune encephalitis.[1] |
Normal cell count and protein do not exclude CSF-restricted oligoclonal bands or a relevant CSF antibody. Conversely, inflammatory CSF alone does not establish an autoimmune cause.[3]
Serum and Routine Blood Tests
Autoimmune encephalitis has no diagnostic routine blood-test pattern. Blood studies help identify complications, associated conditions, and alternative explanations.[1]
| Test | Relevant finding or purpose |
|---|---|
| Complete blood count | May be normal or show nonspecific abnormalities; helps assess infection, systemic illness, and baseline hematological status. |
| Electrolytes, especially sodium | Hyponatremia is particularly associated with leucine-rich glioma-inactivated protein 1 (LGI1) antibody encephalitis. It can contribute to confusion or seizures but does not confirm the diagnosis. |
| Glucose | Hypoglycemia or severe hyperglycemia may cause or worsen altered mental status. |
| Renal and liver function | Abnormalities may suggest metabolic or systemic contributors and affect subsequent treatment planning. |
| C-reactive protein and erythrocyte sedimentation rate | Nonspecific inflammatory markers; normal or elevated results do not establish or exclude autoimmune encephalitis. |
| Selected metabolic, endocrine, and nutritional studies | Thyroid function tests, vitamin B12, ammonia, or other tests may be appropriate when the history and examination suggest an alternative or contributing disorder.[1] |
Neural Antibody Testing
Autoimmune encephalitis antibody testing should generally examine paired serum and CSF. The preferred specimen and diagnostic performance differ between antibodies. Testing only serum or using a restricted panel can miss clinically relevant results.[4]
| Antibody or target | Important laboratory interpretation |
|---|---|
| N-methyl-D-aspartate receptor (NMDAR) | Disease-specific testing identifies IgG against NMDAR subunit 1 (GluN1). CSF is especially important; isolated serum reactivity requires caution and appropriate confirmation in a compatible syndrome.[3] |
| LGI1 | Serum may be more sensitive than CSF. Negative CSF testing alone does not exclude compatible LGI1 antibody encephalitis. |
| Contactin-associated protein-like 2 (CASPR2) | Serum may be more sensitive. Interpret results with the phenotype, specimen, assay, and level of reactivity. |
| Glial fibrillary acidic protein (GFAP) | CSF is preferred for evaluating a compatible autoimmune GFAP astrocytopathy syndrome, which can overlap with or resemble other encephalitic presentations.[1] |
| Other neuronal surface or synaptic targets | Depending on the presentation and laboratory panel, these may include alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), gamma-aminobutyric acid type A receptor (GABAAR), gamma-aminobutyric acid type B receptor (GABABR), and dipeptidyl-peptidase-like protein 6 (DPPX). The list is not exhaustive.[5] |
| 65-kilodalton isoform of glutamic acid decarboxylase (GAD65) | Low serum levels can occur outside neurological autoimmunity. Higher levels or evidence of intrathecal antibody synthesis may support neurological relevance, but results remain syndrome- and assay-dependent.[4] |
| Selected paraneoplastic antibodies | Examples include Hu, also termed antineuronal nuclear antibody type 1 (ANNA-1); Ma2 (paraneoplastic antigen Ma2); and collapsin response-mediator protein 5 (CRMP5; also known as CV2). Confirmed results can support an associated neurological syndrome and direct tumor investigation; clinical correlation remains essential.[1] |
Assay Methods and Specimen Timing
Autoimmune encephalitis antibody evaluation may combine cell-based assays (CBAs) with tissue indirect immunofluorescence (TIIF) or immunohistochemistry (IHC). Complementary methods improve interpretation and can help investigate unexpected results.[4][2]
- Choose targeted tests or a clinically appropriate panel in consultation with the laboratory; comprehensive panels are often useful because syndromes overlap.
- Collect serum and CSF before immunotherapy when feasible, especially before intravenous immunoglobulin (IVIG), which can affect antibody and CSF results. Record treatment received before collection.
- Do not delay urgent care while awaiting antibody results.
- A positive result in an incompatible syndrome, or a negative result despite strong clinical suspicion, warrants specialist and laboratory review.[1]
Infectious Studies
Autoimmune encephalitis evaluation requires parallel investigation for infection. The tests selected depend on the presentation, immune status, exposure history, and local epidemiology.[5]
- Herpes simplex virus (HSV) testing of CSF using polymerase chain reaction (PCR). An early negative result may require repeat testing if suspicion for HSV encephalitis remains high.
- Varicella zoster virus (VZV) testing when appropriate; test selection and interpretation may require specialist advice.
- CSF Gram stain and bacterial culture, with additional fungal, mycobacterial, or other pathogen studies when indicated.
- Blood cultures when systemic infection is suspected.
- Human immunodeficiency virus (HIV) and syphilis testing according to the clinical context and diagnostic pathway.[5]
Additional Tests for Selected Presentations
Autoimmune encephalitis laboratory evaluation should be broadened when findings suggest another inflammatory, demyelinating, neoplastic, or toxic disorder.
- Serum myelin oligodendrocyte glycoprotein (MOG) and aquaporin-4 (AQP4) antibodies may be appropriate in suspected demyelinating or overlapping syndromes.[3]
- Systemic autoimmune serology should be guided by evidence of a systemic connective-tissue disease or vasculitis, rather than interpreted as proof of autoimmune encephalitis.
- CSF cytology and flow cytometry may help when neoplastic involvement is suspected; they are not substitutes for neural antibody testing.
- Toxicology and additional metabolic studies should follow the clinical history and examination.
- Hepatitis, HIV, and tuberculosis screening may be needed for immunotherapy planning. These tests assess treatment-related infection risks rather than establish autoimmune encephalitis.[1]
Children and Adolescents
Autoimmune encephalitis testing in children requires age-appropriate interpretation and attention to developmental, infectious, genetic, and metabolic mimics. Antibody selection should reflect pediatric disease patterns, including consideration of MOG-associated presentations.[6]
Interpretation Pitfalls and Repeat Testing
Autoimmune encephalitis laboratory results require interpretation within the complete clinical picture:
- A positive antibody is not automatically causal. Diagnostic value depends on the antibody, clinical probability, specimen, and assay. A 2024 nationwide study demonstrated important differences in testing performance across antibodies and specimens.[7]
- A negative panel does not establish antibody-negative autoimmune encephalitis. That diagnosis requires the relevant clinical and objective criteria, adequate testing, and exclusion of alternatives.[2]
- Thyroid antibodies and nonspecific voltage-gated potassium channel (VGKC)-complex antibodies do not confirm autoimmune encephalitis. Target-specific LGI1 and CASPR2 testing is preferable to an undifferentiated VGKC-complex result.[1]
- Persistent antibodies do not necessarily mean active disease. Antibody titers alone should not determine relapse or treatment escalation.[3]
- Repeat testing is selective. The 2026 United Kingdom (UK) Joint Societies guideline recommends considering repeat antibody testing when a core phenotype remains convincing despite initially negative serum and CSF results, with specialist advice about additional assays.[5]
Related Microchapters
- Diagnostic study of choice
- Clinical diagnostic criteria
- Antibody-negative disease
- Differential diagnosis
References
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 Hahn C, Budhram A, Alikhani K; et al. (2024). "Canadian Consensus Guidelines for the Diagnosis and Treatment of Autoimmune Encephalitis in Adults". Canadian Journal of Neurological Sciences. 51 (6): 734–754. doi:10.1017/cjn.2024.16. PMID 38312020 Check
|pmid=value (help). - ↑ 2.0 2.1 2.2 Dalmau J, Graus F (2023). "Diagnostic criteria for autoimmune encephalitis: utility and pitfalls for antibody-negative disease". The Lancet Neurology. 22 (6): 529–540. doi:10.1016/S1474-4422(23)00083-2. PMID 37210100 Check
|pmid=value (help). - ↑ 3.0 3.1 3.2 3.3 3.4 Graus F, Titulaer MJ, Balu R; et al. (2016). "A clinical approach to diagnosis of autoimmune encephalitis". The Lancet Neurology. 15 (4): 391–404. doi:10.1016/S1474-4422(15)00401-9. PMID 26906964.
- ↑ 4.0 4.1 4.2 Budhram A, Dubey D, Sechi E; et al. (2020). "Neural Antibody Testing in Patients with Suspected Autoimmune Encephalitis". Clinical Chemistry. 66 (12): 1496–1509. doi:10.1093/clinchem/hvaa254. PMID 33221892 Check
|pmid=value (help). - ↑ 5.0 5.1 5.2 5.3 Michael BD, Huang Y, McKeever S; et al. (2026). "Management of suspected infectious and autoimmune encephalitis in adults – National Guidelines from the United Kingdom Joint Societies". Journal of Infection: 106873. doi:10.1016/j.jinf.2026.106873. PMID 42863638 Check
|pmid=value (help). - ↑ Cellucci T, Van Mater H, Graus F; et al. (2020). "Clinical approach to the diagnosis of autoimmune encephalitis in the pediatric patient". Neurology: Neuroimmunology & Neuroinflammation. 7 (2): e663. doi:10.1212/NXI.0000000000000663. PMID 31953309.
- ↑ Kerstens J, Schreurs MWJ, de Vries JM; et al. (2024). "Autoimmune Encephalitis and Paraneoplastic Neurologic Syndromes: A Nationwide Study on Epidemiology and Antibody Testing Performance". Neurology: Neuroimmunology & Neuroinflammation. 11 (6): e200318. doi:10.1212/NXI.0000000000200318. PMID 39467237 Check
|pmid=value (help).