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Mimics and Diagnostic Pitfalls of Anti-Adenylate Kinase 5 Limbic Encephalitis
Jierui Wang1, Tong Yi1, Guoyu Wang2,3
1Department of Neurology, West China Hospital of Sichuan University, Chengdu, China.
Background:
The clinical understanding of limbic encephalitis associated with antibodies against adenylate kinase 5 (AK5) remains limited. Misinterpretation of antibody test results may lead to diagnostic errors and inappropriate management. We aim to assess the frequency of anti-AK5 encephalitis overdiagnosis and identify common diagnostic pitfalls.
Methods:
Cases of confirmed and mimicking anti-AK5 limbic encephalitis from January 2021 to July 2024 using established criteria for autoimmune encephalitis (AE) were reviewed. AK5 mimics were defined as patients initially suspected of AE with a positive AK5 autoantibody result, but who ultimately received an alternative final diagnosis.
Results:
A total of 21 patients were included (57.1% female; median age 34 years; range 14-82). Only 3 patients (14%) were diagnosed with definite anti-AK5 limbic encephalitis, while 18 patients (86%) were classified as AK5 mimics. Serum autoantibodies were predominantly of the IgG3 subclass, with titers ranging from 1:10 to 1:100. The mimics included primary psychiatric disorders (22%), central nervous system (CNS) infections (22%), other inflammatory disorders (28%), epilepsy (16%), neurodegenerative diseases (6%) and metabolic encephalopathy (6%). The most frequent confounding factor in misdiagnosis was the presence of prominent psychiatric and behavioral symptoms, seen in 50% (9 of 18) of AK5 mimics. The second most common confounder was the presence of low serum antibody titers or isolated serum positivity without corresponding cerebrospinal fluid (CSF) findings (< 1:100), observed in 94% (17 of 18) of mimics.
Conclusion:
Mimics of anti-AK5 encephalitis are common and that misdiagnosis is often driven by non-specific symptoms and clinically irrelevant antibody results.
Insights
Overdiagnosis of anti-adenylate kinase 5 (AK5) encephalitis is common, with most cases being mimics. Non-specific symptoms and low antibody titers often lead to misdiagnosis, highlighting the need for careful interpretation of anti-AK5 antibody results.
Area of Science:
- Neurology
- Immunology
- Diagnostic Medicine
Background:
- Clinical understanding of limbic encephalitis associated with antibodies against adenylate kinase 5 (AK5) is limited.
- Misinterpretation of anti-AK5 antibody test results can lead to diagnostic errors and inappropriate patient management.
- Assessing the frequency of anti-AK5 encephalitis overdiagnosis and identifying diagnostic pitfalls is crucial.
Purpose of the Study:
- To evaluate the incidence of overdiagnosis in anti-AK5 limbic encephalitis.
- To identify common diagnostic challenges and confounding factors in anti-AK5 encephalitis diagnosis.
- To improve the accuracy of diagnosing anti-AK5 limbic encephalitis.
Main Methods:
- Review of confirmed and mimicking anti-AK5 limbic encephalitis cases from January 2021 to July 2024.
- Application of established criteria for autoimmune encephalitis (AE).
- Definition of AK5 mimics as patients with initial AE suspicion and positive anti-AK5 autoantibody but an alternative final diagnosis.
Main Results:
- Out of 21 patients, only 14% had definite anti-AK5 limbic encephalitis; 86% were classified as AK5 mimics.
- Common mimics included psychiatric disorders, CNS infections, other inflammatory conditions, epilepsy, neurodegenerative diseases, and metabolic encephalopathy.
- Key misdiagnosis factors were non-specific psychiatric/behavioral symptoms (50% of mimics) and low serum antibody titers or isolated serum positivity without CSF correlation (94% of mimics).
Conclusions:
- Mimics of anti-AK5 encephalitis are frequently encountered in clinical practice.
- Misdiagnosis is often driven by non-specific clinical symptoms.
- Clinically irrelevant antibody results, such as low titers or isolated serum positivity, contribute significantly to diagnostic errors.
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