Autoimmune Encephalitis screening for an associated neoplasm
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Julinka Auta Fernandes
|
Autoimmune Encephalitis Microchapters |
|
Differentiating Autoimmune Encephalitis from Other Conditions |
|---|
|
Diagnosis |
|
Treatment |
|
Case Studies |
|
Autoimmune Encephalitis On the Web |
Overview
Autoimmune encephalitis may occur with an underlying neoplasm, including a benign ovarian teratoma. Screening seeks a potentially relevant tumor; it does not mean that every patient has cancer. The 2024 Canadian consensus recommends initial neoplasm screening in all adults presenting with autoimmune encephalitis, without waiting for neuronal antibody results.[1]
Clinical Assessment
- Assess age, smoking history, previous malignancy, constitutional symptoms, neurological phenotype, and antibody findings.
- Interpret antibody results alongside the clinical syndrome. An antibody result alone does not establish a paraneoplastic neurological syndrome.
- If a detected tumor is atypical for the antibody or neurological presentation, consider whether a second tumor could be responsible.[2]
Initial Investigations in Adults
Computed Tomography
- Contrast-enhanced computed tomography (CT) of the chest, abdomen, and pelvis is a reasonable initial investigation in adults.
- CT may miss small breast or testicular tumors; additional targeted imaging may be required.
- Select alternatives when pregnancy, impaired renal function, contrast allergy, or radiation exposure affects the investigation choice.[3]
Targeted Imaging
- Ovarian assessment: Perform pelvic ultrasound when ovarian teratoma is suspected. Choose transabdominal or transvaginal examination according to age, clinical circumstances, and consent. Pelvic magnetic resonance imaging (MRI) can clarify negative or equivocal ultrasound when suspicion persists.
- Breast assessment: Use mammography when appropriate; breast MRI may be considered if initial imaging is negative despite substantial suspicion.
- Testicular assessment: Perform testicular ultrasound when the phenotype or antibody suggests a testicular neoplasm.[3]
The 2026 United Kingdom joint societies guideline supports tumor investigation in autoimmune encephalitis associated with tumor-related neuronal surface or intracellular antibodies, with CT, positron emission tomography (PET), mammography, and targeted ultrasound selected according to the suspected primary tumor.[4]
Whole-Body Positron Emission Tomography
Whole-body fluorine-18 fluorodeoxyglucose PET, usually combined with CT (18F-FDG PET/CT), may help identify an occult tumor when conventional investigations are negative but suspicion remains high.[3] This is distinct from brain PET used to investigate encephalitis. PET has limited sensitivity for ovarian teratoma; pelvic ultrasound or MRI remains important.[1]
Antibody-Directed Tumor Search
The following associations guide investigation; they do not imply that a tumor is present in every antibody-positive patient.[5][2]
| Antibody | Important tumor associations |
|---|---|
| N-methyl-D-aspartate receptor (NMDAR) | Ovarian teratoma, particularly in postpubertal females |
| Gamma-aminobutyric acid type B receptor (GABAB receptor) | Lung cancer, especially small-cell lung cancer |
| Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) | Lung cancer, breast cancer, and thymoma |
| Contactin-associated protein-like 2 (CASPR2) | Thymoma, particularly with Morvan syndrome |
| Hu, also called antineuronal nuclear antibody type 1 (ANNA-1) | Small-cell lung cancer |
| Collapsin response-mediator protein 5 (CRMP5; also called CV2) | Small-cell lung cancer and thymoma |
| Paraneoplastic antigen Ma2 (Ma2) | Testicular germ-cell tumors, particularly in younger men; other tumors occur |
| Kelch-like protein 11 (KLHL11) | Testicular germ-cell tumors, particularly seminoma |
Screening in Children
The international pediatric NMDAR antibody encephalitis consensus recommends an early tumor search in all affected children. Tumors are less frequent in prepubertal children and boys, but are not absent. In children younger than five years, neural crest tumors should also be considered.[6]
Abdominal and pelvic ultrasound or MRI, with appropriate chest imaging, should be selected by the pediatric team. Repeat investigation is particularly important with failure to improve or relapse, with continued ovarian teratoma surveillance emphasized in postpubertal females. Adult CT protocols should not automatically be applied to every child.[6]
Follow-Up After Negative Initial Screening
| Clinical situation | Published recommendation |
|---|---|
| High-risk phenotype with a high-risk neuronal antibody | The 2021 paraneoplastic neurological syndrome criteria recommend repeat screening every 4–6 months for 2 years. Similar surveillance applies to selected patients with a high-risk phenotype, an intermediate-risk antibody, and additional risk factors.[2] |
| Intermediate-risk or high-risk antibodies | The 2024 Canadian consensus recommends screening every 3–6 months for at least 2 years, individualized according to risk. Exact frequency and duration are not universally agreed.[1] |
| Low-risk antibody and negative initial screening | Routine repeated tumor screening is generally unnecessary under the Canadian consensus; reassess if the clinical situation changes.[1] |
| Antibody-negative disease | The optimal surveillance schedule is unknown. Consider repeat screening with definite limbic encephalitis, refractory or relapsing disease, or significant cancer risk factors.[1] |
These schedules reflect different consensus frameworks. Choose surveillance according to the patient's phenotype, antibody, demographics, and prior investigations; they do not require repeated whole-body CT in every patient.[2][1]
Limitations and Management of Abnormal Findings
- A negative initial investigation cannot exclude a small or subsequently detectable tumor.[2]
- Conventional serum tumor markers have limited value as a general screening strategy and do not replace imaging.[1]
- A suspicious lesion requires appropriate specialist assessment and, when indicated, tissue diagnosis. Further treatment and surveillance depend on tumor type. Benign tumors may require surgical management without oncological therapy.[1]
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 Hahn C, Budhram A, Alikhani K, et al. Canadian Consensus Guidelines for the Diagnosis and Treatment of Autoimmune Encephalitis in Adults. Can J Neurol Sci. 2024;51(6):734–754. doi:10.1017/cjn.2024.16. PMID:38312020.
- ↑ 2.0 2.1 2.2 2.3 2.4 Graus F, Vogrig A, Muñiz-Castrillo S, et al. Updated Diagnostic Criteria for Paraneoplastic Neurologic Syndromes. Neurol Neuroimmunol Neuroinflamm. 2021;8(4):e1014. doi:10.1212/NXI.0000000000001014. PMID:34006622.
- ↑ 3.0 3.1 3.2 Abboud H, Probasco JC, Irani S, et al. Autoimmune encephalitis: proposed best practice recommendations for diagnosis and acute management. J Neurol Neurosurg Psychiatry. 2021;92(7):757–768. doi:10.1136/jnnp-2020-325300. PMID:33649022.
- ↑ Michael BD, Huang Y, McKeever S, et al. Management of suspected infectious and autoimmune encephalitis in adults – National Guidelines from the United Kingdom Joint Societies. J Infect. 2026:106873. doi:10.1016/j.jinf.2026.106873. PMID:42863638.
- ↑ Graus F, Titulaer MJ, Balu R, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol. 2016;15(4):391–404. doi:10.1016/S1474-4422(15)00401-9. PMID:26906964.
- ↑ 6.0 6.1 Nosadini M, Thomas T, Eyre M, et al. International Consensus Recommendations for the Treatment of Pediatric NMDAR Antibody Encephalitis. Neurol Neuroimmunol Neuroinflamm. 2021;8(5):e1052. doi:10.1212/NXI.0000000000001052. PMID:34301820.