Autoimmune Encephalitis screening
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
Autoimmune encephalitis screening requires distinction between symptom-driven evaluation for encephalitis and investigation for an associated neoplasm. Current guidelines emphasize assessment of compatible clinical syndromes and appropriate tumor investigation; they do not establish a routine population-screening program for asymptomatic individuals.[1][2]
In patients with autoimmune encephalitis, a negative initial tumor screen may need to be followed by surveillance when the phenotype and antibodies indicate increased cancer risk.[3]
Screening
Screening of asymptomatic individuals
Autoimmune encephalitis has no established asymptomatic screening interval in the cited diagnostic guidelines. Clinical assessment should determine whether neuronal antibody testing is appropriate.[1] A 2025 retrospective clinical cohort documented low true-positive yield and frequent false-positive intracellular neuronal antibody results, supporting careful patient selection and interpretation. This study evaluated clinical testing, rather than population screening.[4]
- An isolated positive serum neuronal antibody result does not establish autoimmune encephalitis. Conversely, negative antibody testing does not exclude antibody-negative autoimmune encephalitis.[2]
- When autoimmune encephalitis is clinically suspected, antibody testing should generally include both serum and cerebrospinal fluid, interpreted with the clinical syndrome and other investigations.[2]
Symptom-driven case identification
Autoimmune encephalitis should be considered when subacute memory impairment, altered mental status, or psychiatric symptoms are accompanied by otherwise unexplained seizures, focal neurological findings, or supportive inflammatory investigations.[2]
- After herpes simplex encephalitis: New deterioration warrants investigation for secondary autoimmune encephalitis and persistent or recurrent infection. Detection of neuronal antibodies after infection, without a compatible clinical syndrome, is insufficient for diagnosis.[1]
- During or after immune checkpoint inhibitor treatment: New confusion, seizures, behavioral change, or focal neurological symptoms warrant prompt evaluation for immune-related encephalitis and alternative causes, including infection and cancer involvement of the nervous system.[5]
These presentations require diagnostic evaluation, which may include brain magnetic resonance imaging (MRI), electroencephalography (EEG), cerebrospinal fluid studies, and neuronal antibodies, with exclusion of alternative causes. MRI and routine cerebrospinal fluid findings can be normal in some autoimmune encephalitis subtypes.[2]
Initial screening for an associated neoplasm
Autoimmune encephalitis warrants initial neoplasm screening in all adult presentations according to the Canadian consensus; screening should not be delayed while awaiting neuronal antibody results.[6] The 2026 United Kingdom (UK) guideline also recommends tumor investigation when neuronal surface or intracellular antibodies have a recognized tumor association.[1]
Initial investigation commonly includes contrast-enhanced computed tomography (CT) of the chest, abdomen, and pelvis, supplemented by directed imaging. Imaging choice should account for age, pregnancy, contraindications, clinical phenotype, and the suspected tumor.[7]
| Clinical or antibody context | Investigation |
|---|---|
| N-methyl-D-aspartate receptor (NMDAR) antibody encephalitis with possible ovarian teratoma | Pelvic ultrasound using an appropriate transabdominal or transvaginal approach; pelvic MRI when ultrasound is equivocal or further assessment is needed.[7] |
| Ma2 (paraneoplastic antigen Ma2)- or kelch-like protein 11 (KLHL11)-associated syndrome with possible testicular neoplasm | Testicular ultrasound and specialist-directed further investigation when suspicion persists.[7] |
| Possible breast carcinoma | Mammography; breast MRI if mammography is negative and clinical suspicion remains high.[7] |
| Possible small cell lung carcinoma or thymic tumor | Chest CT as part of the initial body survey.[7] |
- Negative initial imaging with continuing cancer concern: Consider whole-body fluorodeoxyglucose positron emission tomography (FDG-PET)/CT, particularly with intermediate- or high-risk antibodies or selected antibody-negative presentations. FDG-PET has limited sensitivity for ovarian teratoma; pelvic ultrasound or MRI remains important.[6]
- Blood tumor markers: Conventional markers such as carcinoembryonic antigen have limited screening value and do not replace imaging.[6]
- An atypical known tumor: If an identified tumor does not fit the neurological phenotype or antibody association, investigate the possibility of a second tumor.[3]
Repeat neoplasm screening
Autoimmune encephalitis surveillance after a negative initial tumor investigation should be individualized. Consensus recommendations differ slightly in their intervals and qualifying risk groups:
| Guidance | Patients or circumstances | Suggested interval and duration |
|---|---|---|
| 2021 international paraneoplastic neurological syndrome criteria | High-risk neurological phenotype together with high-risk antibodies; also selected high-risk phenotypes with intermediate-risk antibodies and additional risk indicators, such as older age or smoking. | Repeat every 4–6 months for 2 years, adapted to individual risk and clinical evolution.[3] |
| 2024 Canadian adult autoimmune encephalitis consensus | Intermediate- or high-risk antibodies. | Repeat every 3–6 months for at least 2 years; exact surveillance frequency and duration remain uncertain.[6] |
- With lower-risk antibodies and a comprehensive negative initial investigation, routine repeated tumor screening is generally unnecessary unless additional concerns arise. Refractory or relapsing disease can justify renewed investigation.[3]
- For antibody-negative autoimmune encephalitis, the optimal surveillance schedule is unknown. Consider repeat screening with limbic encephalitis, refractory or relapsing disease, or substantial malignancy risk.[6]
Children and adolescents
Autoimmune encephalitis tumor investigation in children should follow the specific syndrome and age-associated risk. The international pediatric NMDAR encephalitis consensus recommends an early tumor search in all children with NMDAR antibody encephalitis, despite the lower tumor frequency in boys and prepubertal children.[8]
- Recommended modalities include abdominal and pelvic ultrasound or MRI, with chest CT or MRI as appropriate.
- Consider ovarian teratoma and, in children younger than 5 years, neural crest tumors.
- Repeat the tumor search with failure to improve or relapse. Longitudinal ovarian teratoma surveillance deserves particular attention in postpubertal females.[8]
References
- ↑ 1.0 1.1 1.2 1.3 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). - ↑ 2.0 2.1 2.2 2.3 2.4 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.
- ↑ 3.0 3.1 3.2 3.3 Graus F, Vogrig A, Muñiz-Castrillo S; et al. (2021). "Updated Diagnostic Criteria for Paraneoplastic Neurologic Syndromes". Neurology: Neuroimmunology & Neuroinflammation. 8 (4): e1014. doi:10.1212/NXI.0000000000001014. PMID 34006622 Check
|pmid=value (help). - ↑ Ford H, Seery N, Tan T; et al. (2025). "Indications and Diagnostic Yield of Paraneoplastic and Autoimmune Encephalitis Antibody Testing: A Retrospective Cohort Study". Brain and Behavior. 15 (8): e70779. doi:10.1002/brb3.70779. PMID 40847447 Check
|pmid=value (help). - ↑ Guidon AC, Burton LB, Chwalisz BK; et al. (2021). "Consensus disease definitions for neurologic immune-related adverse events of immune checkpoint inhibitors". Journal for ImmunoTherapy of Cancer. 9 (7): e002890. doi:10.1136/jitc-2021-002890. PMID 34281989 Check
|pmid=value (help). - ↑ 6.0 6.1 6.2 6.3 6.4 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). - ↑ 7.0 7.1 7.2 7.3 7.4 Abboud H, Probasco JC, Irani S; et al. (2021). "Autoimmune encephalitis: proposed best practice recommendations for diagnosis and acute management". Journal of Neurology, Neurosurgery & Psychiatry. 92 (7): 757–768. doi:10.1136/jnnp-2020-325300. PMID 33649022 Check
|pmid=value (help). - ↑ 8.0 8.1 Nosadini M, Thomas T, Eyre M; et al. (2021). "International Consensus Recommendations for the Treatment of Pediatric NMDAR Antibody Encephalitis". Neurology: Neuroimmunology & Neuroinflammation. 8 (5): e1052. doi:10.1212/NXI.0000000000001052. PMID 34301820 Check
|pmid=value (help).